RIKEN Center for Sustainable Resource Science Drug Discovery Chemistry Platform Unit
Unit Leader: Hiroo Koyama (Ph.D.)
Research Summary

The main focus of our unit is to identify small molecule drug candidates suitable for animal safety studies and subsequent human clinical trials. Our dedicated scientists conduct lead compound generation, and multi-dimensional lead compound optimization on potency to target receptor/enzyme, PKPD profiles, and off-target activities through SAR development. By capitalizing on RIKEN's available expertise in X-ray crystal structure analysis, in-silico modeling studies, and HTS, we strive to expedite the drug discovery process by rational drug design. Our current therapeutic targets include rare genetic diseases and hard-to-treat cancers.
Main Research Fields
- Chemistry
Related Research Fields
- Medicine, Dentistry & Pharmacy
Keywords
- Drug discovery
- Medicinal chemistry
- Pharmacokinetics optimization
Selected Publications
- 1.
Shibata, N.; Cho, N.; Koyama, H.; Naito, N.
"Development of a degrader against oncogenic fusion protein FGFR3-TACC3"
Bioorg. Med. Chem. Lett., 60. 128584. (2022) - 2.
Cho, N.; Kikuzato, K.; Futamura, Y.; Shimuzu, T.; Hayase, H.; Kamisaka, K.; Takaya, D.; Yuki, H.; Honma, T.; Niikura, M.; Kobayashi, F.; Watanabe, N.; Osada, H.; Koyama, H.
"New antimalarials identified by a cell-based phenotypic approach: Structure-activity relationships of 2,3,4,9-tetrahydro-1H-b-carboline derivatives possessing 2-((coumarin-5-yl)oxy)alkanoyl moiety"
Bioorg. Med. Chem., 66, 116830. (2022) - 3.Koda Y.; Sato S.; Yamamoto H.; Niwa H; Watanabe C.; Sato T; Watanabe H.; Nakamura K.; Tanaka A.; Shirouzu M.; Honma T.; Fukami T.; Koyama H.; Umehara T.
"In silico design and synthesis of tranylcypromine-derived LSD1 inhibitors with improved hERG and microsomal stability profiles."
ACS Med. Chem. Lett., 13, 848. (2022) - 4.
Yamamoto, H.; Sakai, N.; Ohte, S.; Sato, T.; Sekimata, K.; Matsumoto, T.; Nakamura, K.; Watanabe, H.; Mishima-Tsumagari, C.; Takaka, A.; Hashizume, Y.; Honma, T.; Katagiri, T.; Miyazono, K.; Tomoda, H.; Shirouzu, M.; Koyama, H.
"Novel bicyclic pyrazoles as potent ALK2 (R206H) inhibitors for the treatment of fibrodysplasia ossificans progressive"
Bioorg. Med. Chem. Lett., 28, 127858. (2021) - 5.
Nara, T.; Nakagawa, Y.; Tsuganezawa, K.; Yuki, H.; Sekimata, K.; Koyama, H.; Ogawa, N.; Honma, T.; Shirouzu, M.; Fukami, T.; Matsuo, Y.; Inaoka, D. K.; Kita, Y.; Tanaka, A.
"The ubiquinone synthesis pathway is a promising drug target for Chagas disease"
PLoS ONE, 16(2), e0243855. (2021) - 6.Sekimata, K.; Sato, T.; Sakai, N.
"ALK2: A Therapeutic Target for Fibrodysplasia Ossificans Progressiva and Diffuse Intrinsic Pontine Glioma."
Chem. Pharm. Bull., 68(3) 194-200. (2020) - 7.
Shirai, F.; Mizutani, A.; Yashiroda, Y.; Tsumura, T.; Kano, Y.; Muramatsu, Y.; Chikada, T.; Yuki, H.; Niwa, H.; Sato, S.; Washizuka, K.; Koda, Y.; Mazaki, Y.; Jan, M-K.; Yoshida, H.; Nagamori, A.; Okue, M.; Watanabe, T.; Kitamura, K.; Shitara, E.; Honma, T.; Umehara, T.; Shirouzu, M.; Fukami, T.; Seimiya, H.; Yoshida, M.; Koyama, H.
"Design and Discovery of an Orally Efficacious Spiroindolinone-based Tankyrase Inhibitor for the Treatment of Colon Cancer."
J. Med. Chem., 63, 4183-4204. (2020) - 8.Sekimata, K.; Sato, T.; Sakai, N.; Watanabe, H.; Mishima-Tsumagari, C.; Taguri, T.; Matsumoto, T.; Fujii, Y.; Handa, N.; Honma, T.; Tanaka, A.; Shirouzu, M.; Yokoyama, S.; Miyazono, K.; Hashizume, Y.; Koyama, H.
"Bis-Heteroaryl Pyrazoles: Identification of Orally Bioavailable Inhibitors of Activin Receptor-Like Kinase-2 (R206H)."
Chem. Pharm. Bull., 67, 224–235. (2019) - 9.
Shirai, F.; Tsumura, T.; Yashiroda, Y.; Yuki, H.; Niwa, H.; Sato, S.; Chikada, T.; Koda, Y.; Washizuka, K.; Yoshimoto, N.; Abe, M.; Onuki, T.; Mazaki, Y.; Hirama, C.; Fukami, T.; Watanabe, H.; Honma, T.; Umehara, T.; Shirouzu, M.; Okue, M.; Kano, Y.; Watanabe, T.; Kitamura, K.; Shitara, E.; Muramatsu, Y.; Yoshida, H.; Mizutani, A.; Seimiya, H.; Yoshida, M; Koyama, H.
"Discovery of Novel Spiroindoline Derivatives as Selective Tankyrase Inhibitors."
J. Med. Chem., 62(7), 3407-3427. (2019) - 10.
Tsuganezawa, K.; Sekimata, K.; Nakagawa, Y.; Utata, R.; Nakamura, K.; Ogawa, N.; Koyama, H.; Shirouzu, M.; Fukami, T.; Kita, K.; Tanaka, A.
"Identification of small molecule inhibitors of human COQ7."
Bioog. Med. Chem. , https://doi.org/10.1016/j.bmc.2019.115182. (2019)
Related Links
Lab Members
Principal investigator
- Hiroo Koyama
- Unit Leader
Core members
- Fumiyuki Shirai
- Senior Research Scientist
- Nobuo Cho
- Senior Research Scientist
- Junichi Kazami
- Senior Technical Scientist
- Katsuhiko Sekimata
- Research Scientist
- Yasuko Koda
- Research Scientist
- Hirokazu Kubota
- Research Scientist
- Hirofumi Yamamoto
- Research Scientist
- Ko Kikuzato
- Senior Technical Staff
- Rie Osaki
- Technical Staff I
- Takuya Tashiro
- Visiting Scientist
- Fumiko Kyotani
- Research Part-time Worker II
- Chieko Shida
- Assistant
Contact Information
Main Research Building room 628
2-1 Hirosawa
Wako, Saitama
351-0198 Japan
Email: hiroo.koyama [at] riken.jp