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Sci Rep. 2019 Dec 20;9(1):19585. doi: 10.1038/s41598-019-55069-y.

A prospective compound screening contest identified broader inhibitors for Sirtuin 1.

Author information

1
Education Academy of Computational Life Sciences (ACLS), Tokyo Institute of Technology, 4259 Nagatsutacho, Midori-ku, Yokohama, 226-8501, Japan.
2
Advanced Computational Drug Discovery Unit, Tokyo Institute of Technology, J3-23-4259 Nagatsutacho, Midori-ku, Yokohama, 226-8501, Japan.
3
RIKEN Medical Sciences Innovation Hub Program, 1-7-22, Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Japan.
4
Department of Computer Science, School of Computing, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro-ku, Tokyo, 152-8550, Japan.
5
Bienta/Enamine Ltd., 78 Chervonotkatska Street 78, Kyiv, 02094, Ukraine.
6
Research Fellow of the Japan Society for the Promotion of Science DC1, Tokyo, Japan.
7
Division of Biomedical Science, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba-shi, Ibaraki, 305-8575, Japan.
8
Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo, 105-8512, Japan.
9
Department of Biological Science, Purdue University, West Lafayette, Indiana, 47907, USA.
10
Department of Computer Science, Purdue University, Indiana, 47907, USA.
11
Department of Biological Sciences, Chuo University, 1-13-27 Kasuga, Bunkyo-ku, Tokyo, 112-8551, Japan.
12
Discovery technology research department, Research division, Chugai Pharmaceutical Co.,Ltd., 200, Kajiwara, Kamakura, Kanagawa, 247-8530, Japan.
13
Okinawa Institute of Science and Technology Graduate University, 1919-1 Tancha, Onna-son, Kunigami, Okinawa, 904-0495, Japan.
14
The Systems Biology Research Institute, Falcon Building 5F, 5-6-9 Shirokanedai, Minato-ku, Tokyo, 108-0071, Japan.
15
Center for Integrative Medical Sciences, RIKEN, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama City, Kanagawa, 230-0045, Japan.
16
Graduate School of Humanities and Sciences, Ochanomizu University, 2-1-1 Otsuka, Bunkyo-ku, Tokyo, 112-8610, Japan.
17
Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8654, Japan.
18
Center for Simulation Science and Informational Biology, Ochanomizu University, 2-1-1 Otsuka, Bunkyo-ku, Tokyo, 112-8610, Japan.
19
School of Advanced Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo, 169-8555, Japan.
20
IMSBIO Co., Ltd., Level 6 OWL TOWER, 4-21-1 Higashi-Ikebukuro, Toshima-ku, Tokyo, 170-0013, Japan.
21
Department of Biotechnology, Bhupat Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai, 600036, Tamilnadu, India.
22
CAS in Crystallography and Biophysics and Bioinformatics Facility, University of Madras, Chennai, 600025, Tamilnadu, India.
23
Okazaki City Hall, 2-9 Juo-cho Okazaki, Aichi, 444-8601, Japan.
24
IQVIA Services Japan K.K., 4-10-18 Takanawa Minato-ku, Tokyo, 108-0074, Japan.
25
Institute for Chemical Research, Kyoto University, Uji, Kyoto, 611-0011, Japan.
26
Training Program of Leaders for Integrated Medical System (LIMS), Kyoto University, Sakyo-ku, Kyoto, 606-8501, Japan.
27
Department of Chemistry & Biotechnology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8654, Japan.
28
Biomodeling Research Co., Ltd., 1-704-2 Uedanishi, Tenpaku-ku, Nagoya, 468-0058, Japan.
29
Faculty of Medicine, Akita University, 1-1-1 Hondo, Akita, 010-8543, Japan.
30
Isotope Science Center, The University of Tokyo, 2-11- 16, Yayoi, Bunkyo-ku, Tokyo, 113-0032, Japan.
31
Department of Biotechnology, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-8657, Japan.
32
Google Japan Inc., 6-10-1 Roppongi, Minato-ku, Tokyo, 106-6126, Japan.
33
Otemachi Bldg. 3F, 1-6-1, Preferred Networks, Otemachi, Chiyoda-ku, Tokyo, 100-0004, Japan.
34
Department of Computational Science and Engineering, Nagoya University, Furocho, Chikusa-ku, Nagoya, 464-8603, Japan.
35
Tosei General Hospital, 160 Nishioiwake-cho, Seto, Aichi, 489-8642, Japan.
36
Department of Complex Systems Science, Graduate School of Information Science, Nagoya University, Furocho, Chikusa, Nagoya, 464-8601, Japan.
37
National Institutes for Biomedical Innovation, Health and Nutrition, Osaka, 567-0085, Japan.
38
RIKEN Center for Biosystems Dynamic Research, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan.
39
Molecular Profiling Research Center for Drug Discovery, National Institute of Advanced Industrial Science and Technology, 2-4-7 Aomi, Koto-ku, Tokyo, 135-0064, Japan.
40
Initiative for Parallel Bioinformatics, Level 14 Hibiya Central Building, 1-2-9 Nishi-Shimbashi Minato-Ku, Tokyo, 105-0003, Japan.
41
Education Academy of Computational Life Sciences (ACLS), Tokyo Institute of Technology, 4259 Nagatsutacho, Midori-ku, Yokohama, 226-8501, Japan. sekijima@c.titech.ac.jp.
42
Department of Computer Science, School of Computing, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro-ku, Tokyo, 152-8550, Japan. sekijima@c.titech.ac.jp.
43
Advanced Computational Drug Discovery Unit, Tokyo Institute of Technology, J3-23-4259 Nagatsutacho, Midori-ku, Yokohama, 226-8501, Japan. sekijima@c.titech.ac.jp.
44
Initiative for Parallel Bioinformatics, Level 14 Hibiya Central Building, 1-2-9 Nishi-Shimbashi Minato-Ku, Tokyo, 105-0003, Japan. sekijima@c.titech.ac.jp.

Abstract

Potential inhibitors of a target biomolecule, NAD-dependent deacetylase Sirtuin 1, were identified by a contest-based approach, in which participants were asked to propose a prioritized list of 400 compounds from a designated compound library containing 2.5 million compounds using in silico methods and scoring. Our aim was to identify target enzyme inhibitors and to benchmark computer-aided drug discovery methods under the same experimental conditions. Collecting compound lists derived from various methods is advantageous for aggregating compounds with structurally diversified properties compared with the use of a single method. The inhibitory action on Sirtuin 1 of approximately half of the proposed compounds was experimentally accessed. Ultimately, seven structurally diverse compounds were identified.

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