KINDAI UNIVERSITY


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KAWASHITA Norihito

Profile

FacultyDepartment of Life Science / Graduate School of Science and Engineering Research
PositionLecturer
DegreePh. D. in Pharmaceutical Sciences
Commentator Guidehttps://www.kindai.ac.jp/meikan/2112-kawashita-norihito.html
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Last Updated :2020/04/05

Research Activities

Research Areas

  • Life sciences, Virology
  • Life sciences, Pharmaceuticals - chemistry and drug development
  • Life sciences, Pharmaceuticals - analytical and physicochemistry
  • Life sciences, Pharmaceuticals - chemistry and drug development

Published Papers

  • Genetic and genomic basis of the mismatch repair system involved in Lynch syndrome, Tamura K, Kaneda M, Futagawa M, Takeshita M, Kim S, Nakama M, Kawashita N, Tatsumi-Miyajima J, Int J Clin Oncol., Int J Clin Oncol., 24(9), 999 - 1011, Sep. 2019 , Refereed
  • PB2 mutations arising during H9N2 influenza evolution in the Middle East confer enhanced replication and growth in mammals., Arai Y, Kawashita N, Ibrahim MS, Elgendy EM, Daidoji T, Ono T, Takagi T, Nakaya T, Matsumoto K, Watanabe Y, PLoS Pathog, PLoS Pathog, 15(7), e1007919, Jul. 2019 , Refereed
  • Three-Dimensional Classification Structure-Activity Relationship Analysis Using Convolutional Neural Network., Moriwaki H, Tian YS, Kawashita N, Takagi T, Chem Pharm Bull, Chem Pharm Bull, 67(5), 426 - 432, May 2019 , Refereed
  • Multiple polymerase gene mutations for human adaptation occurring in Asian H5N1 influenza virus clinical isolates., Arai Y, Kawashita N, Hotta K, Hoang PVM, Nguyen HLK, Nguyen TC, Vuong CD, Le TT, Le MTQ, Soda K, Ibrahim MS, Daidoji T, Takagi T, Shioda T, Nakaya T, Ito T, Hasebe F, Watanabe Y, Scientific reports, Scientific reports, 8(1), 13066, Aug. 2018 , Refereed
  • Characterization of H5N1 Influenza Virus Quasispecies with Adaptive Hemagglutinin Mutations from Single-Virus Infections of Human Airway Cells., Watanabe Y, Arai Y, Kawashita N, Ibrahim MS, Elgendy EM, Daidoji T, Kajikawa J, Hiramatsu H, Sriwilaijaroen N, Ono T, Takagi T, Takahashi K, Shioda T, Matsumoto K, Suzuki Y, Nakaya T, Journal of virology, Journal of virology, 92(11), Jun. 2018 , Refereed
  • Mordred: a molecular descriptor calculator, Hirotomo Moriwaki, Yu-Shi Tian, Norihito Kawashita, Tatsuya Takagi, J. Cheminformatics, J. Cheminformatics, 10(4), 4, Feb. 2018 , Refereed
  • Dengue Virus and Its Inhibitors: A Brief Review., Tian YS, Zhou Y, Takagi T, Kameoka M, Kawashita N, Chemical & pharmaceutical bulletin, Chemical & pharmaceutical bulletin, 66(3), 191 - 206, 2018 , Refereed
  • In silico analysis of enantioselective binding of immunomodulatory imide drugs to cereblon, Takahiro Murai, Norihito Kawashita, Norihito Kawashita, Yu Shi Tian, Tatsuya Takagi, Tatsuya Takagi, SpringerPlus, SpringerPlus, 5(1), 1122, Dec. 01 2016 , Refereed
    Summary:© 2016, The Author(s). Background: Thalidomide and its analogs, lenalidomide and pomalidomide (referred to as immunomodulatory imide drugs or IMiDs) have been known to treat multiple myeloma and other hematologic malignancies as well as to cause teratogenicity. Recently the protein cereblon was identified as the primary target of IMiDs, and crystallographic studies of the cereblon–IMiDs complex showed strong enantioselective binding for the (S)-enantiomer of IMiDs. Results: Using the structures of cereblon and IMiDs [both (S)-enantiomers and (R)-enantiomers] we performed docking simulations in order to replicate this enantiomeric selectivity and to identify the region(s) contributing to this selectivity. We confirmed the enantioselective binding of IMiDs to cereblon with high accuracy, and propose that the hairpin connecting the β10–β11 region of cereblon (residues 351–355) contributes to this selectivity and to the increased affinity with IMiDs. Conclusions: Our docking results provide novel insights into the binding mode of IMiD-like molecules and contribute to a deeper understanding of cereblon-related biology.
  • Novel Polymerase Gene Mutations for Human Adaptation in Clinical Isolates of Avian H5N1 Influenza Viruses, Yasuha Arai, Yasuha Arai, Yasuha Arai, Norihito Kawashita, Norihito Kawashita, Tomo Daidoji, Madiha S. Ibrahim, Madiha S. Ibrahim, Emad M. El-Gendy, Emad M. El-Gendy, Tatsuya Takagi, Tatsuya Takagi, Kazuo Takahashi, Yasuo Suzuki, Kazuyoshi Ikuta, Takaaki Nakaya, Tatsuo Shioda, Yohei Watanabe, Yohei Watanabe, Yohei Watanabe, PLoS Pathogens, PLoS Pathogens, 12(4), e1005583, Apr. 01 2016 , Refereed
    Summary:© 2016 Arai et al. A major determinant in the change of the avian influenza virus host range to humans is the E627K substitution in the PB2 polymerase protein. However, the polymerase activity of avian influenza viruses with a single PB2-E627K mutation is still lower than that of seasonal human influenza viruses, implying that avian viruses require polymerase mutations in addition to PB2-627K for human adaptation. Here, we used a database search of H5N1 clade 2.2.1 virus sequences with the PB2-627K mutation to identify other polymerase adaptation mutations that have been selected in infected patients. Several of the mutations identified acted cooperatively with PB2-627K to increase viral growth in human airway epithelial cells and mouse lungs. These mutations were in multiple domains of the polymerase complex other than the PB2-627 domain, highlighting a complicated avian-to-human adaptation pathway of avian influenza viruses. Thus, H5N1 viruses could rapidly acquire multiple polymerase mutations that function cooperatively with PB2-627K in infected patients for optimal human adaptation.
  • Characterization of two anti-dengue human monoclonal antibodies prepared from PBMCs of patients with dengue illness in Thailand, Z. Y. Li, Z. Y. Li, A. Yamashita, N. Kawashita, T. Sasaki, Y. Pan, K. I. Ono, K. Ikuta, Y. G. Li, Acta Virologica, Acta Virologica, 60, 166 - 173, Jan. 01 2016
    Summary:The global spread of the four dengue virus (DENV) serotypes (dengue-1 to -4) has made this virus a major and growing public health concern. Generally, pre-existing neutralizing antibodies derived from primary infection play a significant role in protecting against subsequent infection with the same serotype. By contrast, these pre-existing antibodies are believed to mediate a non-protective response to subsequent heterotypic DENV infections, leading to the onset of dengue illness. In this study, two monoclonal antibodies prepared by using peripheral blood mononuclear cells (PBMCs) from patients with dengue fever were characterized. Epitope mapping revealed that amino acid residues 254-278 in domain II of the viral envelope protein E were the target region of these antibodies. A database search revealed that certain sequences in this epitope region showed high conservation among the four serotypes of DENV. These two human monoclonal antibodies could neutralize DENV-2,-4 more effectively than DENV-1,-3. The amino acid sequences could not explain this difference in neutralizing activity. However, the 3D structure results showed that amino acid 274 could be the critical residue for the difference in neutralization. These results may provide basic information for the development of a dengue vaccine.
  • Novel Concepts for Drug Hypersensitivity Based on the Use of Long-Time Scale Molecular Dynamic Simulation, Murai Takahiro, Kawashita Norihito, Tian Yu-Shi, Takagi Tatsuya, JOURNAL OF PHARMACEUTICS, JOURNAL OF PHARMACEUTICS, 2016, 9520361, 2016 , Refereed
  • Characterization of H5N1 influenza virus variants with hemagglutinin mutations isolated from patients, Yohei Watanabe, Yohei Watanabe, Yasuha Arai, Tomo Daidoji, Norihito Kawashita, Norihito Kawashita, Madiha S. Ibrahim, Emad El Din, M El-Gendy, Hiroaki Hiramatsu, Ritsuko Kubota-Koketsu, Tatsuya Takagi, Tatsuya Takagi, Takeomi Murata, Kazuo Takahashi, Yoshinobu Okuno, Takaaki Nakaya, Yasuo Suzuki, Kazuyoshi Ikuta, mBio, mBio, 6, Apr. 07 2015
    Summary:© 2015 Watanabe et al. A change in viral hemagglutinin (HA) receptor binding specificity from α 2,3- to α 2,6-linked sialic acid is necessary for highly pathogenic avian influenza (AI) virus subtype H5N1 to become pandemic. However, details of the human-adaptive change in the H5N1 virus remain unknown. Our database search of H5N1 clade 2.2.1 viruses circulating in Egypt identified multiple HA mutations that had been selected in infected patients. Using reverse genetics, we found that increases in both human receptor specificity and the HA pH threshold for membrane fusion were necessary to facilitate replication of the virus variants in human airway epithelia. Furthermore, variants with enhanced replication in human cells had decreased HA stability, apparently to compensate for the changes in viral receptor specificity and membrane fusion activity. Our findings showed that H5N1 viruses could rapidly adapt to growth in the human airway microenvironment by altering their HA properties in infected patients and provided new insights into the human-adaptive mechanisms of AI viruses. IMPORTANCE Circulation between bird and human hosts may allow H5N1 viruses to acquire amino acid changes that increase fitness for human infections. However, human-adaptive changes in H5N1 viruses have not been adequately investigated. In this study, we found that multiple HA mutations were actually selected in H5N1-infected patients and that H5N1 variants with some of these HA mutations had increased human-type receptor specificity and increased HA membrane fusion activity, both of which are advantageous for viral replication in human airway epithelia. Furthermore, HA mutants selected during viral replication in patients were likely to have less HA stability, apparently as a compensatory mechanism. These results begin to clarify the picture of the H5N1 human-adaptive mechanism. IMPORTANCE Circulation between bird and human hosts may allow H5N1 viruses to acquire amino acid changes that increase fitness for human infections. However, human-adaptive changes in H5N1 viruses have not been adequately investigated. In this study, we found that multiple HA mutations were actually selected in H5N1-infected patients and that H5N1 variants with some of these HA mutations had increased human-type receptor specificity and increased HA membrane fusion activity, both of which are advantageous for viral replication in human airway epithelia. Furthermore, HA mutants selected during viral replication in patients were likely to have less HA stability, apparently as a compensatory mechanism. These results begin to clarify the picture of the H5N1 human-adaptive mechanism.
  • Oxidative rearrangement of cyclobutanone derived N,O-ketals leading to pyrrolidone derivatives, Kenichi Murai, Daisuke Endo, Norihito Kawashita, Norihito Kawashita, Tatsuya Takagi, Tatsuya Takagi, Hiromichi Fujioka, Chemical and Pharmaceutical Bulletin, Chemical and Pharmaceutical Bulletin, 63(4), 245 - 247, Apr. 01 2015
    Summary:© 2015 The Pharmaceutical Society of Japan. A halogen-induced oxidative rearrangement of N,O-ketals prepared from cyclobutanones, leading to pyrrolidone derivatives, is developed. The reaction proceeds via an iminium ether intermediate and, depending on the reaction medium, two types of pyrrolidone derivative, containing a halogen atom or hydroxyl group, can be obtained.
  • > A Mini-review on Chemoinformatics Approaches for Drug Discover, KAWASHITA Norihito, KAWASHITA Norihito, YAMASAKI Hiroyuki, MIYAO Tomoyuki, KAWAI Kentaro, SAKAE Yoshitake, ISHIKAWA Takeshi, MORI Kenichi, NAKAMURA Shinya, KANEKO Hiromasa, J Comput Aided Chem (Web), J Comput Aided Chem (Web), 16, 15-29 (J-STAGE), 2015
  • A small compound targeting the interaction between nonstructural proteins 2B and 3 inhibits dengue virus replication, Sabar Pambudi, Norihito Kawashita, Norihito Kawashita, Supranee Phanthanawiboon, Magot Diata Omokoko, Promsin Masrinoul, Akifumi Yamashita, Kriengsak Limkittikul, Teruo Yasunaga, Tatsuya Takagi, Kazuyoshi Ikuta, Takeshi Kurosu, Biochemical and Biophysical Research Communications, Biochemical and Biophysical Research Communications, 440, 393 - 398, Oct. 25 2013
    Summary:The non-structural protein NS2B/NS3 serine-protease complex of the dengue virus (DENV) is required for the maturation of the viral polyprotein. Dissociation of the NS2B cofactor from NS3 diminishes the enzymatic activity of the complex. In this study, we identified a small molecule inhibitor that interferes with the interaction between NS2B and NS3 using structure-based screening and a cell-based viral replication assay. A library containing 661,417 small compounds derived from the Molecular Operating Environment lead-like database was docked to the NS2B/NS3 structural model. Thirty-nine compounds with high scores were tested in a secondary screening using a cell-based viral replication assay. SK-12 was found to inhibit replication of all DENV serotypes (EC 50 =0.74-4.92μM). In silico studies predicted that SK-12 pre-occupies the NS2B-binding site of NS3. Steady-state kinetics using a fluorogenic short peptide substrate demonstrated that SK-12 is a noncompetitive inhibitor against the NS2B/NS3 protease. Inhibition to Japanese encephalitis virus by SK-12 was relatively weak (EC 50 =29.81μM), and this lower sensitivity was due to difference in amino acid at position 27 of NS3. SK-12 is the promising small-molecule inhibitor that targets the interaction between NS2B and NS3. © 2013 Elsevier Inc.
  • Emerging Antigenic Variants at the Antigenic Site Sb in Pandemic A(H1N1)2009 Influenza Virus in Japan Detected by a Human Monoclonal Antibody, Mayo Yasugi, Mayo Yasugi, Mayo Yasugi, Ritsuko Kubota-Koketsu, Ritsuko Kubota-Koketsu, Ritsuko Kubota-Koketsu, Akifumi Yamashita, Norihito Kawashita, Anariwa Du, Anariwa Du, Ryo Misaki, Ryo Misaki, Motoki Kuhara, Motoki Kuhara, Naphatsawan Boonsathorn, Naphatsawan Boonsathorn, Kazuhito Fujiyama, Kazuhito Fujiyama, Yoshinobu Okuno, Takaaki Nakaya, Takaaki Nakaya, Kazuyoshi Ikuta, Kazuyoshi Ikuta, PLoS ONE, PLoS ONE, 8, Oct. 16 2013
    Summary:The swine-origin pandemic A(H1N1)2009 virus, A(H1N1)pdm09, is still circulating i n parts of the human population. To monitor variants that may escape from vaccination specificity, antigenic characterization of circulating viruses is important. In this study, a hybridoma clone producing human monoclonal antibody against A(H1N1)pdm09, designated 5E4, was prepared using peripheral lymphocytes from a vaccinated volunteer. The 5E4 showed viral neutralization activity and inhibited hemagglutination. 5E4 escape mutants harbored amino acid substitutions (A189T and D190E) in the hemagglutinin (HA) protein, suggesting that 5E4 recognized the antigenic site Sb in the HA protein. To study the diversity of Sb in A(H1N1)pdm09, 58 viral isolates were obtained during the 2009/10 and 2010/11 winter seasons in Osaka, Japan. Hemagglutination-inhibition titers were significantly reduced against 5E4 in the 2010/11 compared with the 2009/10 samples. Viral neutralizing titers were also significantly decreased in the 2010/11 samples. By contrast, isolated samples reacted well to ferret anti-A(H1N1)pdm09 serum from both seasons. Nonsynonymous substitution rates revealed that the variant Sb and Ca2 sequences were being positively selected between 2009/10 and 2010/11. In 7,415 HA protein sequences derived from GenBank, variants in the antigenic sites Sa and Sb increased significantly worldwide from 2009 to 2013. These results indicate that the antigenic variants in Sb are likely to be in global circulation currently. © 2013 Yasugi et al.
  • A Practical Estimation Method for Analyzing Adverse Drug Reactions Using Data Mining, Yuko Shirakuni, Kousuke Okamoto, Etuko Uejima, Etuko Uejima, Shigeki Inui, Shigeki Inui, Jun ichi Takahara, Takanori Ohgaru, Takanori Ohgaru, Hiroyuki Yamasaki, Hiroyuki Yamasaki, Yushi Tian, Norihito Kawashita, Norihito Kawashita, Ran Inoue, Teruo Yasunaga, Tatsuya Takagi, Tatsuya Takagi, Therapeutic Innovation and Regulatory Science, Therapeutic Innovation and Regulatory Science, 47, 235 - 241, Mar. 01 2013
    Summary:This study aimed to determine the potentially severe chemical properties of drugs that can cause adverse drug reactions (ADRs) such as erythema multiforme (EM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) by using a data mining method. The study data were extracted from the Adverse Event Reporting System database of the FDA. EM was considered a mild reaction, and SJS and TEN were considered severe reactions. In this study, a new concept termed the "risk of aggravation" (ROA) was defined as whether a certain drug is more likely to cause severe adverse reactions than mild ones. Partial least squares and logistic regression analysis were applied using binary response variable ROAs. These analyses correctly predicted 50 of the 72 drugs associated with SJS and/or TEN and 28 of the 38 drugs associated with EM using binary chemical descriptors that are the same as those using the metric chemical descriptors. © The Author(s) 2012.
  • Human Monoclonal Antibodies Broadly Neutralizing against Influenza B Virus, Mayo Yasugi, Mayo Yasugi, Mayo Yasugi, Ritsuko Kubota-Koketsu, Ritsuko Kubota-Koketsu, Ritsuko Kubota-Koketsu, Akifumi Yamashita, Norihito Kawashita, Anariwa Du, Anariwa Du, Tadahiro Sasaki, Tadahiro Sasaki, Mitsuhiro Nishimura, Mitsuhiro Nishimura, Ryo Misaki, Ryo Misaki, Motoki Kuhara, Motoki Kuhara, Naphatsawan Boonsathorn, Naphatsawan Boonsathorn, Kazuhito Fujiyama, Kazuhito Fujiyama, Yoshinobu Okuno, Takaaki Nakaya, Takaaki Nakaya, Takaaki Nakaya, Kazuyoshi Ikuta, Kazuyoshi Ikuta, PLoS Pathogens, PLoS Pathogens, 9, Feb. 01 2013
    Summary:Influenza virus has the ability to evade host immune surveillance through rapid viral genetic drift and reassortment; therefore, it remains a continuous public health threat. The development of vaccines producing broadly reactive antibodies, as well as therapeutic strategies using human neutralizing monoclonal antibodies (HuMAbs) with global reactivity, has been gathering great interest recently. Here, three hybridoma clones producing HuMAbs against influenza B virus, designated 5A7, 3A2 and 10C4, were prepared using peripheral lymphocytes from vaccinated volunteers, and were investigated for broad cross-reactive neutralizing activity. Of these HuMAbs, 3A2 and 10C4, which recognize the readily mutable 190-helix region near the receptor binding site in the hemagglutinin (HA) protein, react only with the Yamagata lineage of influenza B virus. By contrast, HuMAb 5A7 broadly neutralizes influenza B strains that were isolated from 1985 to 2006, belonging to both Yamagata and Victoria lineages. Epitope mapping revealed that 5A7 recognizes 316G, 318C and 321W near the C terminal of HA1, a highly conserved region in influenza B virus. Indeed, no mutations in the amino acid residues of the epitope region were induced, even after the virus was passaged ten times in the presence of HuMAb 5A7. Moreover, 5A7 showed significant therapeutic efficacy in mice, even when it was administered 72 hours post-infection. These results indicate that 5A7 is a promising candidate for developing therapeutics, and provide insight for the development of a universal vaccine against influenza B virus. © 2013 Yasugi et al.
  • Discovery of novel low-molecular-weight HIV-1 inhibitors interacting with cyclophilin A using in silico screening and biological evaluations, Yu Shi Tian, Chris Verathamjamras, Norihito Kawashita, Norihito Kawashita, Kousuke Okamoto, Teruo Yasunaga, Kazuyoshi Ikuta, Masanori Kameoka, Masanori Kameoka, Masanori Kameoka, Tatsuya Takagi, Tatsuya Takagi, Journal of Molecular Modeling, Journal of Molecular Modeling, 19, 465 - 475, Jan. 01 2013
    Summary:Cyclophilin A has attracted attention recently as a new target of anti-human immunodeficiency virus type 1 (HIV-1) drugs. However, so far no drug against HIV-1 infection exhibiting this mechanism of action has been approved. To identify new potent candidates for inhibitors, we performed in silico screening of a commercial database of more than 1,300 drug-like compounds by using receptor-based docking studies. The candidates selected from docking studies were subsequently tested using biological assays to assess anti-HIV activities. As a result, two compounds were identified as the most active. Specifically, both exhibited anti-HIV activity against viral replication at a low concentration and relatively low cytotoxicity at the effective concentration inhibiting viral growth by 50 %. Further modification of these molecules may lead to the elucidation of potent inhibitors of HIV-1. [Figure not available: see fulltext.] © 2012 Springer-Verlag.
  • A practical estimation method for analyzing adverse drug reactions using data mining, Yuko Shirakuni, Kousuke Okamoto, Etsuko Uejima, Shigeki Inui, Jun-ichi Takahara, Takanori Ohgaru, Hiroyuki Yamasaki, YuShi Tian, Norihito Kawashita, Ran Inoue, Teruo Yasunaga, Tatsuya Takagi, Drug Information Journal, Drug Information Journal, Nov. 2012 , Refereed
  • Antigenic analysis of highly pathogenic avian influenza virus H5N1 sublineages co-circulating in Egypt, Yohei Watanabe, Madiha S. Ibrahim, Hany F. Ellakany, Norihito Kawashita, Norihito Kawashita, Tomo Daidoji, Tomo Daidoji, Tatsuya Takagi, Tatsuya Takagi, Teruo Yasunaga, Takaaki Nakaya, Takaaki Nakaya, Takaaki Nakaya, Kazuyoshi Ikuta, Journal of General Virology, Journal of General Virology, 93, 2215 - 2226, Oct. 01 2012
    Summary:Highly pathogenic avian influenza virus H5N1 has spread across Eurasia and Africa, and outbreaks are now endemic in several countries, including Indonesia, Vietnam and Egypt. Continuous circulation of H5N1 virus in Egypt, from a single infected source, has led to significant genetic diversification with phylogenetically separable sublineages, providing an opportunity to study the impact of genetic evolution on viral phenotypic variation. In this study, we analysed the phylogeny of H5 haemagglutinin (HA) genes in influenza viruses isolated in Egypt from 2006 to 2011 and investigated the effect of conserved amino acid mutations in the HA genes in each of the sublineages on their antigenicity. The analysis showed that viruses in at least four sublineages still persisted in poultry in Egypt as of 2011. Using reverse genetics to generate HA-reassortment viruses with specific HA mutations, we found antigenic drift in the HA in two influenza virus sublineages, compared with the other currently co-circulating influenza virus sublineages in Egypt. Moreover, the two sublineages with significant antigenic drift were antigenically distinguishable. Our findings suggested that phylogenetically divergent H5N1 viruses, which were not antigenically cross-reactive, were co-circulating in Egypt, indicating that there was a problem in using a single influenza virus strain as seed virus to produce influenza virus vaccine in Egypt and providing data for designing more efficacious control strategies in H5N1-endemic areas. © 2012 SGM.
  • Compliance Survey for Thalidomide Safety Use (part5); after Revision of TERMS, Shirakuni Yuko, Hattori Chizuko, Yamaguchi Nobuyasu, Kubo Teruyoshi, Kawashita Norihito, Takagi Tatsuya, Nasu Masao, PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, 21, 208, Aug. 2012 , Refereed
  • Frequency of D222G and Q223R hemagglutinin mutants of pandemic (H1N1) 2009 influenza virus in Japan between 2009 and 2010, Mayo Yasugi, Mayo Yasugi, Shota Nakamura, Shota Nakamura, Tomo Daidoji, Tomo Daidoji, Norihito Kawashita, Norihito Kawashita, Ririn Ramadhany, Ririn Ramadhany, Cheng Song Yang, Cheng Song Yang, Teruo Yasunaga, Tetsuya Iida, Tetsuya Iida, Toshihiro Horii, Toshihiro Horii, Toshihiro Horii, Kazuyoshi Ikuta, Kazuo Takahashi, Takaaki Nakaya, Takaaki Nakaya, Takaaki Nakaya, PLoS ONE, PLoS ONE, 7, Feb. 17 2012
    Summary:Background: In April 2009, a novel swine-derived influenza A virus (H1N1pdm) emerged and rapidly spread around the world, including Japan. It has been suggested that the virus can bind to both 2,3- and 2,6-linked sialic acid receptors in infected mammals, in contrast to contemporary seasonal H1N1 viruses, which have a predilection for 2,6-linked sialic acid. Methods/Results: To elucidate the existence and transmissibility of α2,3 sialic acid-specific viruses in H1N1pdm, amino acid substitutions within viral hemagglutinin molecules were investigated, especially D187E, D222G, and Q223R, which are related to a shift from human to avian receptor specificity. Samples from individuals infected during the first and second waves of the outbreak in Japan were examined using a high-throughput sequencing approach. In May 2009, three specimens from mild cases showed D222G and/or Q223R substitutions in a minor subpopulation of viruses infecting these individuals. However, the substitutions almost disappeared in the samples from five mild cases in December 2010. The D187E substitution was not widespread in specimens, even in May 2009. Conclusions: These results suggest that α2,3 sialic acid-specific viruses, including G222 and R223, existed in humans as a minor population in the early phase of the pandemic, and that D222 and Q223 became more dominant through human-to-human transmission during the first and second waves of the epidemic. These results are consistent with the low substitution rates identified in seasonal H1N1 viruses in 2008. © 2012 Yasugi et al.
  • Recent Advances in the Development of Small-Molecule Compounds Targeting HIV-1 gp41 as Membrane Fusion Inhibitors, Norihito Kawashita, Yu-Shi Tian, U. Chandimal de Silva, Kousuke Okamoto, Tatsuya Takagi, Mini-Reviews in Organic Chemistry, Mini-Reviews in Organic Chemistry, 9(1), 20 - 26, Feb. 2012 , Refereed
  • Development of Novel Evaluation Method to Anti-influenza Drug Resistance using Docking Study, Kawashita N, Yasuda M, Tian Y.-S, Okamoto K, Kawase M, Yasunaga T, Takagi T, Antiviral Research, Antiviral Research, 90(2), A71, May 2011 , Refereed
  • Acquisition of human-type receptor binding specificity by new H5N1 influenza virus sublineages during their emergence in birds in Egypt, Yohei Watanabe, Madiha S. Ibrahim, Madiha S. Ibrahim, Madiha S. Ibrahim, Hany F. Ellakany, Norihito Kawashita, Norihito Kawashita, Rika Mizuike, Hiroaki Hiramatsu, Nogluk Sriwilaijaroen, Nogluk Sriwilaijaroen, Tatsuya Takagi, Tatsuya Takagi, Yasuo Suzuki, Kazuyoshi Ikuta, PLoS Pathogens, PLoS Pathogens, 7, May 01 2011
    Summary:Highly pathogenic avian influenza A virus subtype H5N1 is currently widespread in Asia, Europe, and Africa, with 60% mortality in humans. In particular, since 2009 Egypt has unexpectedly had the highest number of human cases of H5N1 virus infection, with more than 50% of the cases worldwide, but the basis for this high incidence has not been elucidated. A change in receptor binding affinity of the viral hemagglutinin (HA) from α2,3- to α2,6-linked sialic acid (SA) is thought to be necessary for H5N1 virus to become pandemic. In this study, we conducted a phylogenetic analysis of H5N1 viruses isolated between 2006 and 2009 in Egypt. The phylogenetic results showed that recent human isolates clustered disproportionally into several new H5 sublineages suggesting that their HAs have changed their receptor specificity. Using reverse genetics, we found that these H5 sublineages have acquired an enhanced binding affinity for α2,6 SA in combination with residual affinity for α2,3 SA, and identified the amino acid mutations that produced this new receptor specificity. Recombinant H5N1 viruses with a single mutation at HA residue 192 or a double mutation at HA residues 129 and 151 had increased attachment to and infectivity in the human lower respiratory tract but not in the larynx. These findings correlated with enhanced virulence of the mutant viruses in mice. Interestingly, these H5 viruses, with increased affinity to α2,6 SA, emerged during viral diversification in bird populations and subsequently spread to humans. Our findings suggested that emergence of new H5 sublineages with α2,6 SA specificity caused a subsequent increase in human H5N1 influenza virus infections in Egypt, and provided data for understanding the virus's pandemic potential. © 2011 Watanabe et al.
  • Erratum: Anionic polymer, poly(methyl vinyl ether-maleic anhydride)-coated beads-based capture of human influenza A and B virus (Bioorg. Med. Chem. (2009) 17 (752-757)), Akikazu Sakudo, Koichi Baba, Megumi Tsukamoto, Atsuko Sugimoto, Takashi Okada, Takanori Kobayashi, Norihito Kawashita, Tatsuya Takagi, Kazuyoshi Ikuta, Bioorganic and Medicinal Chemistry, Bioorganic and Medicinal Chemistry, 19, 1010, Jan. 15 2011
  • Recent Advances in the Development of Small-Molecule Compounds Targeting HIV-1 gp41 as Membrane Fusion Inhibitors, Mini-Reviews in Organic Chemistry, Mini-Reviews in Organic Chemistry, in press, 2011
  • Design and evaluation of antiretroviral peptides corresponding to the C-terminal heptad repeat region (C-HR) of human immunodeficiency virus type 1 envelope glycoprotein gp41, Bongkot Soonthornsata, Bongkot Soonthornsata, Bongkot Soonthornsata, Yu Shi Tian, Yu Shi Tian, Yu Shi Tian, Piraporn Utachee, Sompong Sapsutthipas, Panasda Isarangkura-na-ayuthaya, Wattana Auwanit, Tatsuya Takagi, Tatsuya Takagi, Kazuyoshi Ikuta, Kazuyoshi Ikuta, Pathom Sawanpanyalert, Norihito Kawashita, Norihito Kawashita, Masanori Kameoka, Masanori Kameoka, Virology, Virology, 405, 157 - 164, Sep. 01 2010
    Summary:Two α-helical heptad repeats, N-HR and C-HR, located in the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp41, play an important role in membrane fusion by forming a 6-helix bundle. C34, a peptide mimicking C-HR, inhibits the formation of the 6-helix bundle; thus, it has potential as a novel antiretroviral compound. In order to improve the inhibitory effect of C34 on HIV-1 replication, we designed new C34-derived peptides based on computational analysis of the stable conformation of the 6-helix bundle. Newly designed peptides showed a stronger inhibitory effect on the replication of recombinant viruses containing CRF01_AE, subtype B or subtype C Env than C34 or a fusion inhibitor, T-20. In addition, these peptides inhibited the replication of a T-20-resistant virus. We propose that these peptides could be applied to develop novel antiretroviral compounds to inhibit the replication of various subtypes of HIV-1 as well as of T-20-resistant variants. © 2010 Elsevier Inc.
  • Design and evaluation of antiretroviral peptides corresponding to the C-terminal heptad repeat region (C-HR) of human immunodeficiency virus type 1 envelope glycoprotein gp41, Bongkot Soonthornsata, Yu-Shi Tian, Piraporn Utachee, Sompong Sapsutthipas, Panasda Isarangkura-na-ayuthaya, Wattana Auwanit, Tatsuya Takagi, Kazuyoshi Ikuta, Pathom Sawanpanyalert, Norihito Kawashita, Masanori Kameoka, Virology, Virology, 405(1), 157-164, Sep. 2010 , Refereed
    Summary:Two alpha-helical heptad repeats, N-HR and C-HR, located in the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp41, play an important role in membrane fusion by forming a 6-helix bundle. C34, a peptide mimicking C-HR, inhibits the formation of the 6-helix bundle; thus, it has potential as a novel antiretroviral compound. In order to improve the inhibitory effect of C34 on HIV-1 replication, we designed new C34-derived peptides based on computational analysis of the stable conformation of the 6-helix bundle. Newly designed peptides showed a stronger inhibitory effect on the replication of recombinant viruses containing CRF01_AE, subtype B or subtype C Env than C34 or a fusion inhibitor, T-20. In addition, these peptides inhibited the replication of a T-20-resistant virus. We propose that these peptides could be applied to develop novel antiretroviral compounds to inhibit the replication of various subtypes of HIV-1 as well as of T-20-resistant variants.
  • Nonlinear classification of hERG channel inhibitory activity by unsupervised classification method, Shinnosuke Hidaka, Hiroyuki Yamasaki, Yoshihiro Ohmayu, Akiko Matsuura, Kousuke Okamoto, Norihito Kawashita, Norihito Kawashita, Norihito Kawashita, Tatsuya Takagi, Tatsuya Takagi, Tatsuya Takagi, Journal of Toxicological Sciences, Journal of Toxicological Sciences, 35, 393 - 399, Jun. 16 2010
    Summary:The side effects that occur in the central nervous system and circulatory system due to medicines are expected to be prevented by research and development. However, many of the compounds in medicines have the possibility of causing arrhythmia, and methods developed to detect this problem at the early stage of drug development are not always successful. In the present study, we classified drug compounds according to their activity using only structural information. To classify compounds, we used a self-organizing map (SOM), which is a nonlinear unsupervised classification method. We first analyzed a small-scale dataset, and an excellent classification result was obtained. We then applied our method to a large-scale dataset containing numerous inert compounds and were again able to classify the compounds according to their activity. Both classifications showed some compound activity, although a few differences between the two SOM maps were seen.
  • Nonlinear classification of drug-induced arrhythmogenic activity by unsupervised classification method, Shinnosuke HIDAKA, Hiroyuki YAMASAKI, Yoshihiro OHMAYU, Akiko MATSUURA, Kousuke OKAMOTO, Norihito KAWASHITA, Tatsuya TAKAGI, The Journal of Toxicological Sciences, The Journal of Toxicological Sciences, in press, May 2010 , Refereed
    Summary:The side effects that occur in the central nervous system and circulatory system due to medicines are expected to be prevented by research and development. However, many of the compounds in medicines have the possibility of causing arrhythmia, and methods developed to detect this problem at the early stage of drug development are not always successful. In the present study, we classified drug compounds according to their activity using only structural information. To classify compounds, we used a self-organizing map (SOM), which is a nonlinear unsupervised classification method. We first analyzed a small-scale dataset, and an excellent classification result was obtained. We then applied our method to a large-scale dataset containing numerous inert compounds and were again able to classify the compounds according to their activity. Both classifications showed some compound activity, although a few differences between the two SOM maps were seen.
  • Highly conserved sequences for human neutralization epitope on hemagglutinin of influenza A viruses H3N2, H1N1 and H5N1: Implication for human monoclonal antibody recognition, Akifumi Yamashita, Norihito Kawashita, Ritsuko Kubota-Koketsu, Yuji Inoue, Yohei Watanabe, Madiha S Ibrahim, Shoji Ideno, Mikihhiro Yunoki, Yoshinobu Okuno, Tatsuya Takagi, Teruo Yasunaga, Biochemical and Biophysical Research Communications, Biochemical and Biophysical Research Communications, 393(4):614-618(4), 614 - 618, Mar. 19 2010 , Refereed
  • Structure of the prion protein and its gene: An analysis using bioinformatics and computer simulation, Akikazu Sakudo, Akikazu Sakudo, Guangai Xue, Norihito Kawashita, Norihito Kawashita, Yasuhisa Ano, Tatsuya Takagi, Tatsuya Takagi, Tatsuya Takagi, Hideharu Shintani, Yasuharu Tanaka, Takashi Onodera, Kazuyoshi Ikuta, Current Protein and Peptide Science, Current Protein and Peptide Science, 11, 166 - 179, Mar. 01 2010
    Summary:Prion protein (PrP) gene encodes cellular PrP (PrP C ), a glycosylphosphatidylinositol (GPI)-anchored cell membrane protein indispensable for infections of prion, which causes Creutzfeldt-Jakob disease (CJD) in humans, bovine spongiform encephalopathy (BSE) in cattle, and scrapie in sheep. Although PrPC is known to be converted into an abnormal isoform (PrP Sc ) upon prion infection and play an important role in prion diseases, the mechanisms involved remain unclear, partly due to the insolubility of PrP Sc , which prevents experimental biochemical and biophysical analyses. Recently, with improvements in computer power and methods, computer analyses have been contributing more to prion studies. A comparison of PrP gene sequences revealed mutations and polymorphisms in the open reading frame (ORF) of the human PrP gene related to prion diseases. In contrast, little mutations or polymorphisms related to susceptibility to BSE were found in the ORF of the bovine PrP gene, though relationships between insertion/deletion (Ins/Del) polymorphisms of the PrP gene promoter and susceptibility to BSE have been found. Our results have shown that the specific protein 1 (Sp1) plays important role in the activity of PrP gene promoter, which is influenced by polymorphisms in the Sp1 binding sites. The potential structural dynamics of PrP have been simulated by computational methods such as molecular dynamics (MD) and quantum mechanics (QM). The proposed mechanisms of conversion have revealed new insights in prion diseases. In this review, we will introduce the gene structure, polymorphisms, and potential structural dynamics of PrP revealed by basic and advanced computational analyses. The possible contribution of these methods to elucidation of the pathogenicity of prion diseases and functions of PrP C is discussed. © 2010 Bentham Science Publishers Ltd.
  • Ecotoxicity Prediction Using 3D Descriptors, Shinnosuke Hidaka, Hiroaki Shiraishi, Yoshihiro Ohmayu, Hiroyuki Yamasaki, Kousuke Okamoto, Norihito Kawashita, Teruo Yasunaga, Tatsuya Takagi, Journal of Computer Aided Chemistry, Journal of Computer Aided Chemistry, vol.11, 11-18, Feb. 2010 , Refereed
    Summary:A vast quantity of chemicals are present in our environment and are considered indispensable to our high technological society. However, there are some chemicals that are hazardous and that can extensively impact both human health and the global environment. In Japan, ecotoxicity tests of chemical substances have been conducted with the goal of contributing to the Organization for Economic Cooperation and Development (OECD) evaluation program for harmful high-production volume (HPV) chemicals since 1995. To date, only about 500 compounds have been tested. There is a possibility that quantitative structure-activity relationships (QSARs) may enable us to predict environmental toxicities and fates as well as the physical and chemical properties of compounds; therefore, the toxicity prediction by QSARs is a possible alternative to the measurements of their ecotoxicities. In this study, we generated QSAR models from toxicity tests of Daphnids using only 3D descriptors to examine the availability of particular 3D descriptors for predicting of the ecotoxicity of compounds with various structures. Predicton accuracy of the model generated in this study was adequate and improved compared to
  • Structure of the prion protein and its gene: an analysis using bioinformatics and computer simulation, Akikazu Sakudo, G. Xue, Norihito Kawashita, Y. Ano, Tatsuya Takagi, H. Shintani, Y. Tanaka, T. Onodera, Kazuyoshi Ikuta, Current Protein and Peptide Science, Current Protein and Peptide Science, 11(2):166-179, Dec. 2009 , Refereed
  • Signal Detection of Drug Complications Applying Association Rule Learning for Stevens-Johnson Syndrome, Yuko Shirakuni, Kousuke Okamoto, Norihito Kawashita, Teruo Yasunaga, Tatsuya Takagi, Journal of Computer Aided Chemistry, Journal of Computer Aided Chemistry, 10, 118-127, Nov. 2009 , Refereed
    Summary:The adverse events induced by drugs have been complicated, when two or more drugs are administrated for a patient. We selected "Stevens-Johnson Syndrome (SJS) " as a research object, which is one of the severe skin manifestations. The data source is a database constructed by the Food and Drug Administration (FDA). FDA's post-marketing safety surveillance program is supported by the Adverse Event Reporting System (AERS). AERS is designed with a computerized information database. To analyze the relationships between the concurrent medication and SJS in this study, we applied association rule learning. Our purpose is to propose an efficient procedure that enables the detection of signals for drugs related to an adverse event, without assuming the involvement of a specific drug. We defined new value K for the evaluation of existing signal detection. Association rule was evaluated according to criterion K value. As a result, it was suggested to obtain a strong signal by combining two concomitant drugs. Association rule learning in this study was applicable for the analysis of the relationships between adverse events and pairs of drugs.
  • Anionic polymer, poly(methyl vinyl ether-maleic anhydride)-coated beads-based capture of human influenza A and B virus, Akikazu Sakudo, Koichi Baba, Megumi Tsukamoto, Atsuko Sugimoto, Takashi Okada, Takanori Kobayashi, Norihito Kawashita, Tatsuya Takagi, Kazuyoshi Ikuta, Bioorganic and Medicinal Chemistry, Bioorganic and Medicinal Chemistry, in press(2), 752 - 757, Jan. 15 2009 , Refereed
    Summary:An anionic magnetic beads-based method was developed for the capture of human influenza A and B viruses from nasal aspirates, allantoic fluid and culture medium. A
    polymer, poly(methyl vinyl ether-maleic anhydride) [poly(MVE-MA)], was used to endow magnetic beads with a negative charge and bioadhesive properties. After
    incubation with samples containing human influenza virus, the beads were separated from supernatants by applying a magnetic field. The absorption of the virus by the beads was confirmed by hemagglutinin assay, immunochromatography, Western blotting, egg infection, and cell infection. Successful capture was proved using 5 H1N1 influenza A viruses, 10 H3N2 influenza A viruses, and 6 influenza B viruses.
    Furthermore, the infectivity in chicken embryonated eggs and Madin-Darby canine kidney (MDCK) cells of the captured human influenza virus was similar to that of the total viral quantity of starting materials. Therefore, this method of capture using magnetic beads coated with poly(MVE-MA) can be broadly used for the recovery of infectious human influenza viruses.
  • Screening of HIV membrane fusion peptide by using computational chemistry, Kawashita Norihito, JOURNAL OF PHARMACOLOGICAL SCIENCES, JOURNAL OF PHARMACOLOGICAL SCIENCES, 109, 32P, 2009 , Refereed
  • Application of Partial Least Square on Quantitative Analysis of L-, D-, and DL-Tartaric Acid by Terahertz Absorption Spectra, Rika NISHIKIORI, Mariko YAMAGUCHI, Keisuke TAKANO, Tokujiro ENATSU, Masahiko TANI, U. CHANDIMAL de SILVA, Norihito KAWASHITA, Tatsuya TAKAGI, Shotaro MORIMOTO, Masanori HANGYO, Masaya KAWASE, Chemical and Pharmaceutical Bulletin, Chemical and Pharmaceutical Bulletin, 56(3), 305 - 307, Jun. 2008 , Refereed
  • Computational Studies of gp41 6-Helix Bundle: Do Stabilized Energy of HIV Membrane Fusion Inhibitor C34 and Interaction Energy of gp41 6-Helix Bundle have Good Correlation with their Inhibitory Activity?, Kawashita N, Tian Y.-S, Yasuda M, de Silva U. C, Kashiwada R, Nakamura S, Goto N, Nishikiori R, Okamoto K, Kameoka M, Yasunaga T, Kawase M, Ikuta K, Takagi T, Antiviral Research, Antiviral Research, 78(2), A42, (2008), Apr. 2008 , Refereed
  • Enhancement of ordinal CoMFA by ridge logistic partial least squares, Takanori Ohgaru, Takanori Ohgaru, Ryo Shimizu, Kosuke Okamoto, Norihito Kawashita, Norihito Kawashita, Masaya Kawase, Yuko Shirakuni, Rika Nishikiori, Tatsuya Takagi, Tatsuya Takagi, Journal of Chemical Information and Modeling, Journal of Chemical Information and Modeling, 48, 910 - 917, Apr. 01 2008
    Summary:Conventional comparative molecular field analysis (CoMFA) requires at least 3 orders of experimental data, such as IC 50 and K i , to obtain a good model, although practically there are many screening assays where biological activity is measured only by rating scale. To improve three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis, we developed in this study a modified ordinal classification-oriented CoMFA using partial-least-squares generalized linear regression and ridge estimation. The modified Logistic CoMFA was validated using a corticosteroid binding globulin receptor binding data set, a benchmark for 3D-QSAR, and an acetylcholine esterase inhibitor data set. Our results show that modification of Logistic CoMFA enhanced both prediction accuracy and 3D graphical analysis. In addition, the 3D graphical analysis of the modified Logistic CoMFA was much improved. This improvement resulted in more accurate information on the binding mode between proteins and ligands than in the case of conventional CoMFA. © 2008 American Chemical Society.
  • Enhancement of Ordinal CoMFA by Ridge Logistic Partial Least Squares., Takanori Ohgaru, Ryo Shimizu, Kousuke Okamoto, Norihito Kawashita, Masaya Kawase, Yuko Shirakuni, Rika Nishikiori, Tatsuya Takagi, J.Chem.Inf.Model., J.Chem.Inf.Model., 48(4), 910 - 917, Apr. 2008 , Refereed
    Summary:Conventional comparative molecular field analysis (CoMFA) requires at least 3 orders of experimental data, such as IC 50 and K i, to obtain a good model, although practically there are many screening assays where biological activity is measured only by rating scale. To improve three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis, we developed in this study a modified ordinal classification-oriented CoMFA using partial-least-squares generalized linear regression and ridge estimation. The modified Logistic CoMFA was validated using a corticosteroid binding globulin receptor binding data set, a benchmark for 3D-QSAR, and an acetylcholine esterase inhibitor data set. Our results show that modification of Logistic CoMFA enhanced both prediction accuracy and 3D graphical analysis. In addition, the 3D graphical analysis of the modified Logistic CoMFA was much improved. This improvement resulted in more accurate information on the binding mode between proteins and ligands than in the case of conventional CoMFA.
  • Application of partial least square on quantitative analysis of L-, D-, and DL-tartaric acid by terahertz absorption spectra, Rika Nishikiori, Mariko Yamaguchi, Keisuke Takano, Tokujiro Enatsu, Masahiko Tani, U. Chandimal De Silva, Norihito Kawashita, Tatsuya Takagi, Shotaro Morimoto, Masanori Hangyo, Masaya Kawase, Chemical and Pharmaceutical Bulletin, Chemical and Pharmaceutical Bulletin, 56, 305 - 307, Mar. 01 2008
    Summary:Absorption spectra of polycrystalline L-, D-, and DL-tartaric acid have been measured by terahertz time domain spectroscopy (THz-TDS). Different absorption bands are observed for DL-tartaric acid and its enantiomers (L- and D-tartaric acid). This result shows that the THz-TDS can be used for distinguishing between DL-tartaric acid and enantiomers (L- and D-tartaric acid). Moreover, partial least square (PLS) can be found to improve the quantitation of L-tartaric acid in L- and DL-tartaric acid mixture by THz-TDS. © 2008 Pharmaceutical Society of Japan.
  • Development of Fingerprint Verification Type Self-Organized Map Applied to Profiling Seized Methamphetamine., Rika Nishikiori, Yukiko Makino, Yukino Ochi, Noriyuki Yamashita, Kousuke Okamoto, Norihito Kawashita, Jun-ichi Takahara, Teruo Yasunaga, Tatsuya Takagi, Masaya Kawase, J. Comput. Aided Chem., J. Comput. Aided Chem., 9, 30-36, Mar. 2008 , Refereed
  • Regioselective, nucleophilic carbon–carbon bond formation at the C4-position of indoles initiated by the aromatic Pummerer-type reaction, Shuji Akai, Norihito Kawashita, Yasufumi Wada, Hideharu Satoh, Anahita, Hessamian Alinejad, Keisuke Kakiguchi, Ikumi Kuriwaki, Yasuyuki Kita, Tetrahedron Letters, Tetrahedron Letters, 47, 1881-1884, Feb. 2006 , Refereed
    Summary:The treatment of the 5-(phenylsulfinyl)indoles with trifluoroacetic anhydride in the presence of carbon nucleophiles achieved the title reactions with complete regioselectivity.
  • Highly Regioselective NucleophilicCarbon-Carbon Bond Formation on Furans and Thiophenes Initiated by Pummerer-Type Reaction, Shuji Akai, Norihito Kawashita, Hideharu Satoh, Yasufumi Wada, Keisuke Kakiguchi, Ikumi Kuriwaki, Yasuyuki Kita, Organic Letters, Organic Letters, 6, 21, 3793-3796, Sep. 2004 , Refereed
    Summary:The reactions of (phenylsulfinyl)furans or -thiophenes with carbon nucleophiles in the presence of trifluoroacetic anhydride allowed the
    nucleophilic installation of carbon functional groups on the furan and thiophene nuclei with complete regioselectivity.
  • Regioselective synthesis of 2,3,5-trisubstituted indoles from p-sulfinylaniline by dual use of the sulfinyl group, Shuji Akai, Norihito Kawashita, Nobuyoshi Morita, Yuka Nakamura, Kiyosei Iio, Yasuyuki Kita, Heterocycles, Heterocycles, 58, 75 - 78, Nov. 22 2002
    Summary:A novel and convergent synthesis of 2,3,5-trisubstituted indoles (6) from p-sulfinylaniline (1) is described. The single p-sulfinyl group was repeatedly employed in two ways; viz., the construction of the 2,3-disubstituted indole/indoline skeleton and the introduction of a carbon substituent at the C-5 position.

Misc

  • プラズマ処理水中の過硝酸の分解に関する量子化学計算, 川嶋裕介, 川下理日人, 川下理日人, 高木達也, 高木達也, 井川聡, 北野勝久, 応用物理学会春季学術講演会講演予稿集(CD-ROM), 64th, ROMBUNNO.16p‐313‐8,   2017 03 , http://jglobal.jst.go.jp/public/201702257083612462
  • 活性酸素種によるアミノ酸残基への酸化反応機構の量子化学計算, 川嶋裕介, 川下理日人, 川下理日人, 高木達也, 高木達也, 井川聡, 北野勝久, 応用物理学会春季学術講演会講演予稿集(CD-ROM), 64th, ROMBUNNO.16p‐313‐9,   2017 03 , http://jglobal.jst.go.jp/public/201702291920105664
  • Evaluation of Novel Anti-Dengue Candidates Using In Silico and In Vitro Approaches, TIAN Yu‐Shi, MATSUDA Hitoshi, LIU Xinzhe, KAWASHITA Norihito, KAWASHITA Norihito, TAKAGI Tatsuya, TAKAGI Tatsuya, 日本薬学会年会要旨集(CD-ROM), 137th, ROMBUNNO.26G‐ISMS06,   2017 , http://jglobal.jst.go.jp/public/201702242103033242
  • Analyses of protein-ligand interaction of BACE1 and its ligands using fragment molecular orbital method, HASHIMOTO Yuji, KAWASHITA Norihito, MORIWAKI Hirotomo, TIAN Yu‐Shi, TAKAGI Tatsuya, 構造活性相関シンポジウム講演要旨集, 44th, 49‐50,   2016 11 16 , http://jglobal.jst.go.jp/public/201602228635903082
  • Constructing prediction models of adverse drug reactions using machine learning, MORIUCHI Hiroaki, TIAN Yu‐Shi, MORIWAKI Hirotomo, AOKI Satoshi, TAKAYAMA Nobuki, KAWASHITA Norihito, HIBI Takayuki, TAKAGI Tatsuya, 構造活性相関シンポジウム講演要旨集, 44th, 31‐32,   2016 11 16 , http://jglobal.jst.go.jp/public/201602241042520012
  • Novel Polymerase Gene Mutations for Human Adaptation in Clinical Isolates of Avian H5N1 Influenza Viruses, ARAI Yasuha, ARAI Yasuha, KAWASHITA Norihito, DAIDOJI Tomo, IBRAHIM Madiha, TAKAHASHI Kazuo, SUZUKI Yasuo, NAKAYA Takaaki, SHIODA Tatsuo, IKUTA Kazuyoshi, WATANABE Yohei, WATANABE Yohei, 日本ウイルス学会学術集会プログラム・抄録集, 64th, 139,   2016 09 30 , http://jglobal.jst.go.jp/public/201602235500029292
  • 状態空間モデルによるサリドマイド製剤安全管理手順(TERMS)における患者対象調査の時系列データ解析, 加藤平太, 白國優子, 川下理日人, 田雨時, 高木達也, 那須正夫, 社会薬学, 35, Supplement, 111, 111,   2016 08 29 , http://jglobal.jst.go.jp/public/201602213002976341
  • 分子記述子計算ソフトウェアmordredの開発, 森脇寛智, 川下理日人, 川下理日人, TIAN Yu‐Shi, 高木達也, 高木達也, ケモインフォマティクス討論会予稿集(Web), 39th, ROMBUNNO.Y4(J‐STAGE),   2016 , 10.11545/ciqs.2016.0_Y4, http://jglobal.jst.go.jp/public/201602226619679330
  • 分子軌道計算によるスペクトルの精度の検討, 諏訪志典, 川嶋裕介, 川下理日人, 川下理日人, 藤居由基, TIAN Yu‐Shi, 藤岡弘道, 有澤光弘, 高木達也, 高木達也, ケモインフォマティクス討論会予稿集(Web), 39th, ROMBUNNO.P9(J‐STAGE),   2016 , 10.11545/ciqs.2016.0_P9, http://jglobal.jst.go.jp/public/201602252376482162
  • 化合物の光分解性予測モデルの構築に関する基礎的検討, 松山裕美, 川下理日人, 川下理日人, TIAN Yu‐Shi, 岡本晃典, 高木達也, 高木達也, ケモインフォマティクス討論会予稿集(Web), 39th, ROMBUNNO.P16(J‐STAGE),   2016 , 10.11545/ciqs.2016.0_P16, http://jglobal.jst.go.jp/public/201602291732483542
  • フラグメント分子軌道法による病原性蛋白質と宿主因子との相互作用解析, 川下理日人, 川下理日人, TIAN Yu‐Shi, 高木達也, 高木達也, 分子科学討論会講演プログラム&要旨(Web), 10th, ROMBUNNO.3G17 (WEB ONLY),   2016 , http://jglobal.jst.go.jp/public/201702273408507040
  • Chance Correlationを可能な限り回避する回帰手法の開発と応用, 八田朋子, 川下理日人, 川下理日人, 田雨時, 高木達也, 高木達也, ケモインフォマティクス討論会予稿集(Web), 38th, 124‐125(J‐STAGE),   2015 10 01 , 10.11545/ciqs.2015.0_124, http://jglobal.jst.go.jp/public/201502206701780644
  • Novel insights enantioselective binding of IMiDs to cereblon using in silico docking simulations., MURAI Takahiro, KAWASHITA Norihito, TIAN Yushi, TAKAGI Tatsuya, 構造活性相関シンポジウム講演要旨集, 43rd, 52‐55,   2015 09 , http://jglobal.jst.go.jp/public/201502215364318371
  • SPECT脳血流画像に基づく機械学習を用いた疾患判別予測モデルの構築, 阪本健也, 幡生あすか, 高木達也, 岡本晃典, 川下理日人, 日本薬学会年会要旨集(CD-ROM), 135th, 2, ROMBUNNO.27PA-PM010, 289,   2015 03 , http://jglobal.jst.go.jp/public/201502202001941110
  • ドッキングスタディとボルツマン分布を組み合わせた薬剤耐性変異評価法の開発, 上田智弘, 川下理日人, 岡本晃典, 高木達也, 情報化学討論会講演要旨集(Web), 37th, P06(J-STAGE),   2014 11 20 , 10.11545/ciqs.2014.0_P06, http://jglobal.jst.go.jp/public/201502268282962685
  • SPECT脳血流画像に基づく機械学習を用いた疾患判別, 阪本 健也, 幡生 あすか, 岡本 晃典, 川下 理日人, 高木 達也, 日本薬学会年会要旨集, 134年会, 2, 297, 297,   2014 03
  • 【ここまできた!抗ウイルス薬】 3次元定量的構造活性相関(3D-QSAR)を利用した抗HCV薬の探索, 高木 達也, 川下 理日人, ファルマシア, 49, 11, 1090, 1094,   2013 11 , 10.14894/faruawpsj.49.11_1090
  • Identification of a novel inhibitor against dengue virus NS2B/NS3 protease by a structure-based study, SABAR Pambudi, KAWASHITA Norihito, SUPRANEE Phanthanawiboon, MAGOT Omokoko, PROMSIN Masrinoul, KRIENGSAK Limkittikul, YASUNAGA Teruo, TAKAGI Tatsuya, IKUTA Kazuyoshi, KUROSU Takeshi, 日本ウイルス学会学術集会プログラム・抄録集, 61st, 161,   2013 10 29 , http://jglobal.jst.go.jp/public/201302202285639561
  • In Sillico解析を応用したフラビウイルスプロテーゼ阻害剤の同定, Pambudi Sabar, 川下 理日人, 安永 照雄, 高木 達也, Limkittikul Kriengsak, 生田 和良, 黒須 剛, 日本獣医学会学術集会講演要旨集, 156回, 266, 266,   2013 08
  • 薬学部生と既卒者が共に学習できる薬学統計学のeラーニングサイトの構築について, 宮崎 恭行, 村田 俊郎, 岡本 晃典, 川下 理日人, 白井 達也, 上島 悦子, 高木 達也, 日本薬学会年会要旨集, 133年会, 4, 230, 230,   2013 03
  • クラスタリングの反復を用いた生体影響に関するQSARモデルの構築, 河南 潤, 伊藤 光文, 伊藤 雅士, 岡本 晃典, 川下 理日人, 高木 達也, 日本薬学会年会要旨集, 133年会, 2, 201, 201,   2013 03
  • 医薬学データ用統計解析プログラム、MEPHASの更新について(その3), 福井 大介, 田 雨時, 岡本 晃典, 川下 理日人, 後藤 直久, 安永 照雄, 高木 達也, 日本薬学会年会要旨集, 133年会, 2, 323, 323,   2013 03
  • 副作用予測を指向したリバースフィッティングシステムの構築とその医薬品への適用, 長田 真衣, 川下 理日人, 田 雨時, 岡本 晃典, 安永 照雄, 高木 達也, 日本薬学会年会要旨集, 132年会, 4, 159, 159,   2012 03
  • 医薬学データ用統計解析プログラム、MEPHASの更新について(その2), 福井 大介, 田 雨時, 岡本 晃典, 川下 理日人, 後藤 直久, 安永 照雄, 高木 達也, 日本薬学会年会要旨集, 132年会, 4, 161, 161,   2012 03
  • サリドマイド安全使用のための薬剤管理に関する調査(その4), 高木 達也, 白國 優子, 川下 理日人, 平井 啓, 岡本 晃典, 服部 千鶴子, 山口 進康, 那須 正夫, 日本薬学会年会要旨集, 132年会, 4, 290, 290,   2012 03
  • 社会における薬剤リスクに対する認識調査, 服部 千鶴子, 白国 優子, 平井 啓, 須磨 一夫, 岡本 晃典, 川下 理日人, 山口 進康, 高木 達也, 那須 正夫, 日本薬学会年会要旨集, 132年会, 4, 290, 290,   2012 03
  • フラグメント分子軌道法を利用したHIV gp41の相互作用解析, 川下 理日人, 田 雨時, 岡本 晃典, 安永 照雄, 高木 達也, 日本エイズ学会誌, 13, 4, 435, 435,   2011 11
  • シクロフィリンAをターゲットとする新たな候補を見つけるための分子ドッキング法の検討(Investigation of molecular docking method in order to find novel candidates targeting cyclophilin A), 田 雨時, 川下 理日人, 岡本 晃典, Verathamjamras Chris, 安永 照雄, 生田 和良, 亀岡 正典, 高木 達也, 日本エイズ学会誌, 13, 4, 482, 482,   2011 11
  • A Computational Approach to Search Active Peptides as Membrane Fusion Inhibitors of HIV-1, Tian Yu-Shi, Kawashita Norihito, Verathamjamras Chris, Okamoto Kousuke, Yasunaga Teruo, Kameoka Masanori, Takagi Tatsuya, ANTIVIRAL RESEARCH, 90, 2, A76, A77,   2011 05 , Refereed, 10.1016/j.antiviral.2011.03.166
  • 医薬品による副作用予測を目的とした、リバースフィッティングシステムの構築, 長田 真衣, 川下 理日人, 田 雨時, 荒井 由貴, 岡本 晃典, 安永 照雄, 高木 達也, 日本薬学会年会要旨集, 131年会, 4, 125, 125,   2011 03
  • CypAをターゲットとする抗HIV-1低分子化合物のin Silico探索, 田 雨時, 川下 理日人, Chris Verathamjamras, 杉本 裕昌, 岡本 晃典, 安永 照雄, 亀岡 正典, 高木 達也, 日本薬学会年会要旨集, 131年会, 4, 126, 126,   2011 03
  • 医薬学データ用統計解析プログラム、MEPHASの更新について, 福井 大介, 田 雨時, 岡本 晃典, 川下 理日人, 後藤 直久, 安永 照雄, 高木 達也, 日本薬学会年会要旨集, 131年会, 4, 127, 127,   2011 03
  • サリドマイド安全使用のための薬剤管理に関する調査(その2), 高木 達也, 川下 理日人, 白国 優子, 平井 啓, 服部 千鶴子, 岡本 晃典, 藤原 拓也, 山口 進康, 那須 正夫, 日本薬学会年会要旨集, 131年会, 4, 305, 305,   2011 03
  • 要管理医薬品の回収・指導に関する調査, 白國 優子, 藤原 拓也, 須磨 一夫, 平井 啓, 服部 千鶴子, 岡本 晃典, 川下 理日人, 山口 進康, 那須 正夫, 高木 達也, 日本薬学会年会要旨集, 131年会, 4, 305, 305,   2011 03
  • 計量薬学 信頼と保証を科学する 多変量解析法を用いた疾患・副作用の診断、予後予測支援, 高木 達也, 原田 雅史, 高橋 由武, 岡本 晃典, 川下 理日人, 白國 優子, 渡辺 俊輔, 井上 藍, 幡生 あすか, 日本薬学会年会要旨集, 130年会, 1, 210, 210,   2010 03
  • シクロフィリンAを標的としたフラグメントスクリーニングによる抗HIV薬の探索研究, 川下 理日人, 田 雨時, 杉本 裕昌, 岡本 晃典, 安永 照雄, 高木 達也, 日本薬学会年会要旨集, 130年会, 2, 246, 246,   2010 03
  • HIV1膜融合阻害剤としての2-Aryl 5-(4-Oxo-3-phenethyl-2-thioxo thiazolidinylidenemethyl)furansのQSAR解析, 田 雨時, 川下 理日人, 岡本 晃典, 安永 照雄, 高木 達也, 日本薬学会年会要旨集, 130年会, 2, 254, 254,   2010 03
  • 化学物質の環境運命予測を目指した、光分解・加水分解反応データベースの構築, 栗花落 昇平, 岡本 晃典, 尾形 直紀, 川下 理日人, 高原 淳一, 高木 達也, 日本薬学会年会要旨集, 129年会, 3, 264, 264,   2009 03
  • ドッキングスタディを利用したインフルエンザノイラミニダーゼ阻害剤の薬剤耐性評価, 安田 匡志, 川下 理日人, 柏田 理恵, 田 雨時, 岡本 晃典, 川瀬 雅也, 安永 照雄, 高木 達也, 日本薬学会年会要旨集, 129年会, 4, 142, 142,   2009 03
  • A QSAR Study using GA-PLS on anti-HIV-1 Small Molecules Targeting Cyclophilin A, Yushi Tian, Kawashita Norihito, Kashiwada Rie, Sugimoto Hiromasa, Yasunaga Teruo, Okamoto Kousuke, Takagi Tatsuya, PLS '09: PROCEEDINGS OF THE 6TH INTERNATIONAL CONFERENCE ON PARTIAL LEAST SQUARES AND RELATED METHODS, 334, 337,   2009 , Refereed
  • 医薬化学 目指せ!第2世代のHIVインテグラーゼ阻害剤, 川下 理日人, ファルマシア, 44, 12, 1216, 1217,   2008 12
  • Computational studies of gp41 6-helix bundle: Do stabilized energy of HIV membrane fusion inhibitor C34 and interaction energy of gp41 6-helix bundle have good correlation with their inhibitory activity?, Kawashita Norihito, Tian Yu-Shi, Yasuda Masashi, de Silva, U. Chandimal, Kashiwada Rie, Nakamura Shota, Goto Naohisa, Nishikiori Rika, Okamoto Kousuke, Kameoka Masanori, Yasunaga Teruo, Kawase Masaya, Ikuta Kazuyoshi, Takagi Tatsuya, ANTIVIRAL RESEARCH, 78, 2, A42,   2008 05 , Refereed, 10.1016/j.antiviral.2008.01.080
  • HIV膜融合阻害剤C34に関する構造活性相関研究, 川下 理日人, 田 雨時, 安田 匡志, 岡本 晃典, 錦織 理華, 亀岡 正典, 安永 照雄, 生田 和良, 川瀬 雅也, 高木 達也, 日本薬学会年会要旨集, 128年会, 2, 53, 53,   2008 03
  • HIV gp41の蛋白質間相互作用計算によるアミノ酸残基と膜融合阻害活性との相関, 川下 理日人, 田 雨時, 中村 昇太, 岡本 晃典, 後藤 直久, de Silva, U. Chandimal, 亀岡 正典, 川瀬 雅也, 安永 照雄, 生田 和良, 高木 達也, 日本エイズ学会誌, 9, 4, 405, 405,   2007 11
  • Computational Studies on Relationship with Protein-Protein Interaction Energy of HIV-1 gp41 and Its Inhibitory Activity of Membrane Fusion, Kawashita, N, Tian, Y.-s, Nakamura, S, Kawaguchi, A, Yamashita, N, Okamoto, K, de Silva, U. C, Kameoka, M, Yasunaga, T, Ikuta, K, Takagi, T,   2007 01
  • Improvement of nonparametric regression method based on the PLS algorithm., Nishikiori Rika, Yonekura Satoshi, Okamoto Kousuke, Ohgaru Takanori, Matsuura Akiko, Ochi Yukino, Morimoto Shotaro, Saito Tadashi, Kawashita Norihito, Yasunaga Teruo, Kawase Masaya, Takagi Tatsuya, Symposium on Chemical Information and Computer Sciences, 2007, 0, JK03, JK03,   2007 , http://ci.nii.ac.jp/naid/130004574961
    Summary:Since some of the descriptors for QSAR data show nonlinear relationships between the descriptors and biological activities, they should be analyzed by nonlinear analysis methods. However, the algorithm of nonparametric regression methods is complicated and is difficult to show the contributions of QSAR descriptors. Hence, we proposed a new simple nonparametric regression method, which was named SANORA, before. This method is based on the additive model as well as penalized local regression. In addition, this method has comparatively simple algorithm which means that the contributions of predictive variables can be easily estimated. We would like to introduce this method and propose the solution of the overfitting problem when it is applied to the data set which has many predictive variables. In order to avoid this problem and to obtain results faster, we applied the PLS algorithm to reduce dimensions of the data: The latent variables were used as predictive variables for the SANORA analysis of ACE inhibition activity data. As a result of cross-validation, the predictive performance of the constructed model became better.
  • Refinement of Regression Discrimination Analysis, Yamasaki Hiroyuki, Ohgaru Takanori, Okamoto Kousuke, Kawashita Norihito, Takahara Junichi, Nishikiori Rika, Kawase Masaya, Yasunaga Teruo, Takagi Tatsuya, Symposium on Chemical Information and Computer Sciences, 2007, 0, JP19, JP19,   2007 , http://ci.nii.ac.jp/naid/130004574984
    Summary:A method called Regression Discrimination Analysis (RDA) has been developed for the discrimination of ordered categorical data. The method (RDA method) has the advantages of simultaneously considering any numbers of classes and faster computation than other methods. However, the RDA method is not utilized because the RDA method is inferior in recognition and prediction. The RDA method has two problems. First, although the RDA method needs parameters called class values, the class values are not specified. For this reason, the most adequate class values have to be determined for each time. Secondly, the borders of the RDA method are also not specified. The change of the borders has great influence on the result of discrimination. In this study, we suggest the optimized class values which are determined by searching for the normality in the data belonging each class value. We have refined the RDA method to some extent in this study.
  • A Concise Synthesis of Bisbenzannelated Spiroketals via Aromatic Pummerer-type Reaction, Kakiguchi, K, Kuriwaki, I, Dohi, T, Kawashita, N, Akai, S, Kita, Y,   2006 08
  • Synthesis of Polysubstituted Indoles by Iterative Use of the Aromatic Pummerer-type Reaction, Kawashita, N, Kakiguchi, K, Wada, Y, Akai, S, Kita, Y,   2005 08
  • Highly Regioselective, Nucleophilic Substitution on Electron-Sufficient Heteroaromatic Compounds through the Aromatic Pummerer-Type Reaction, Kawashita, N, Akai, S, Kita, Y,   2004 08