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Structure, solubility, and permeability relationships in a diverse middle molecule library.
Miyachi, Hiroyuki; Kanamitsu, Kayoko; Ishii, Mayumi; Watanabe, Eri; Katsuyama, Akira; Otsuguro, Satoko; Yakushiji, Fumika; Watanabe, Mizuki; Matsui, Kouhei; Sato, Yukina; Shuto, Satoshi; Tadokoro, Takashi; Kita, Shunsuke; Matsumaru, Takanori; Matsuda, Akira; Hirose, Tomoyasu; Iwatsuki, Masato; Shigeta, Yasuteru; Nagano, Tetsuo; Kojima, Hirotatsu; Ichikawa, Satoshi; Sunazuka, Toshiaki; Maenaka, Katsumi.
Afiliação
  • Miyachi H; Lead Exploration Unit, Drug Discovery Initiative, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. Electronic address: miyachi_hiroyuki@mol.f.u-tokyo.ac.jp.
  • Kanamitsu K; Lead Exploration Unit, Drug Discovery Initiative, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
  • Ishii M; Lead Exploration Unit, Drug Discovery Initiative, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
  • Watanabe E; Lead Exploration Unit, Drug Discovery Initiative, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
  • Katsuyama A; Center for Research and Education on Drug Discovery, Faculty of Pharmaceutical Science, Hokkaido University, Kita 12, Nishi 6, Kita ku, Sapporo 060 0812, Japan; Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
  • Otsuguro S; Center for Research and Education on Drug Discovery, Faculty of Pharmaceutical Science, Hokkaido University, Kita 12, Nishi 6, Kita ku, Sapporo 060 0812, Japan.
  • Yakushiji F; Center for Research and Education on Drug Discovery, Faculty of Pharmaceutical Science, Hokkaido University, Kita 12, Nishi 6, Kita ku, Sapporo 060 0812, Japan; Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
  • Watanabe M; Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
  • Matsui K; Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
  • Sato Y; Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
  • Shuto S; Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
  • Tadokoro T; Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
  • Kita S; Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
  • Matsumaru T; Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
  • Matsuda A; Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
  • Hirose T; Omura Satoshi Memorial Research Institute, Kitasato University, Shirokane 5-9-1, Minato-ku, Tokyo 108-8641, Japan.
  • Iwatsuki M; Omura Satoshi Memorial Research Institute, Kitasato University, Shirokane 5-9-1, Minato-ku, Tokyo 108-8641, Japan.
  • Shigeta Y; Center for Computational Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577, Japan.
  • Nagano T; Drug Discovery Initiative, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
  • Kojima H; Drug Discovery Initiative, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
  • Ichikawa S; Center for Research and Education on Drug Discovery, Faculty of Pharmaceutical Science, Hokkaido University, Kita 12, Nishi 6, Kita ku, Sapporo 060 0812, Japan; Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan. Electronic address: ichikawa@p
  • Sunazuka T; Omura Satoshi Memorial Research Institute, Kitasato University, Shirokane 5-9-1, Minato-ku, Tokyo 108-8641, Japan. Electronic address: sunazukatoshiaki@yahoo.co.jp.
  • Maenaka K; Center for Research and Education on Drug Discovery, Faculty of Pharmaceutical Science, Hokkaido University, Kita 12, Nishi 6, Kita ku, Sapporo 060 0812, Japan; Global Station for Biosurfaces and Drug Discovery, Hokkaido University, Kita 12, Nishi 6, Kita ku, Sapporo 060 0812, Japan. Electronic addr
Bioorg Med Chem Lett ; 37: 127847, 2021 04 01.
Article em En | MEDLINE | ID: mdl-33571648
To develop methodology to predict the potential druggability of middle molecules, we examined the structure, solubility, and permeability relationships of a diverse library (HKDL ver.1) consisting of 510 molecules (359 natural product derivatives, 76 non-natural products, 46 natural products, and 29 non-natural product derivatives). The library included peptides, depsipeptides, macrolides, and lignans, and 476 of the 510 compounds had a molecular weight in the range of 500-2000 Da. The solubility and passive diffusion velocity of the middle molecules were assessed using the parallel artificial membrane permeability assay (PAMPA). Quantitative values of solubility of 471 molecules and passive diffusion velocity of 287 molecules were obtained, and their correlations with the structural features of the molecules were examined. Based on the results, we propose a method to predict the passive diffusion characteristics of middle molecules from their three-dimensional structural features.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Bibliotecas de Moléculas Pequenas Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2021 Tipo de documento: Article
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Bibliotecas de Moléculas Pequenas Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2021 Tipo de documento: Article