Rentosertib
| Clinical data | |
|---|---|
| Other names | ISM001-055;[1] INS018_055[2][3] |
| Routes of administration | Oral |
| Identifiers | |
| |
| CAS Number | |
| PubChem CID | |
| DrugBank | |
| ChemSpider | |
| UNII | |
| Chemical and physical data | |
| Formula | C27H30FN7O |
| Molar mass | 487.583 g·mol−1 |
| 3D model (JSmol) | |
| |
| |
Rentosertib (also known as ISM001‑055[1] and INS018_055) is an investigational new drug that is being evaluated for the treatment of idiopathic pulmonary fibrosis (IPF). It targets TNIK (TRAF2 and NCK-interacting protein kinase).[1] It is asserted to be the first drug generated entirely by generative artificial intelligence to reach mid-stage human clinical trials, and the first to target a novel AI-discovered biological pathway.[2][4][5]
Development
Rentosertib was developed using a generative AI platform designed to identify novel disease-associated targets and rapidly design optimized small-molecule inhibitors.[1][6][7] TNIK was identified as a central regulator of fibrosis and inflammation in IPF. Rentosertib selectively inhibits TNIK, and progressed from target discovery through phase 0 and 1 clinical trials in under 30 months.[1]
Clinical trials
A multicenter, double-blind, placebo-controlled, randomized phase 2a trial was conducted in China, testing the drug in 71 IPF patients from July 2023 to June 2024, encompassing an administration period of 12 weeks. Participants were randomly assigned to receive 30 mg once daily (QD), 30 mg twice daily (BID), 60 mg QD, or placebo.[1]
The trial's primary endpoint was the incidence of treatment-emergent adverse events (TEAEs).[1]
Nomenclature
In March 2025, the United States Adopted Names (USAN) Council approved "Rentosertib" as the official nonproprietary name for ISM001-055.[6]
References
- ^ a b c d e f g Xu, Zuojun; Ren, Feng; Wang, Ping; Cao, Jie; Tan, Chunting; Ma, Dedong; Zhao, Li; Dai, Jinghong; Ding, Yipeng; Fang, Haohui; Li, Huiping; Liu, Hong; Luo, Fengming; Meng, Ying; Pan, Pinhua; Xiang, Pingchao; Xiao, Zuke; Rao, Sujata; Satler, Carol; Liu, Sang; Lv, Yuan; Zhao, Heng; Chen, Shan; Cui, Hui; Korzinkin, Mikhail; Gennert, David; Zhavoronkov, Alex (2025). "A generative AI-discovered TNIK inhibitor for idiopathic pulmonary fibrosis: a randomized phase 2a trial". Nature Medicine. 31 (8): 2602–2610. doi:10.1038/s41591-025-03743-2. PMC 12353801. PMID 40461817.
- ^ a b Field, Hayden (29 June 2023). "The first fully A.I.-generated drug enters clinical trials in human patients". CNBC.
- ^ Ren, Feng; Aliper, Alex; Chen, Jian; Zhao, Heng; Rao, Sujata; Kuppe, Christoph; Ozerov, Ivan V.; Zhang, Man; Witte, Klaus; Kruse, Chris; Aladinskiy, Vladimir; Ivanenkov, Yan; Polykovskiy, Daniil; Fu, Yanyun; Babin, Eugene; Qiao, Junwen; Liang, Xing; Mou, Zhenzhen; Wang, Hui; Pun, Frank W.; Torres-Ayuso, Pedro; Veviorskiy, Alexander; Song, Dandan; Liu, Sang; Zhang, Bei; Naumov, Vladimir; Ding, Xiaoqiang; Kukharenko, Andrey; Izumchenko, Evgeny; Zhavoronkov, Alex (January 27, 2025). "A small-molecule TNIK inhibitor targets fibrosis in preclinical and clinical models". Nature Biotechnology. 43 (1): 63–75. doi:10.1038/s41587-024-02143-0. PMC 11738990. PMID 38459338.
- ^ Chik H (13 March 2024). "World's first AI-developed drug for deadly lung disease enters landmark clinical trials in China, US". South China Morning Post.
- ^ Li S, Yue R, Lu S, Luo JC, Wu X, Zhang Z, Liu M, Fan Y, Zhang Y, Pan C, Huang X (July 2025). "Artificial Intelligence and Machine Learning in Acute Respiratory Distress Syndrome Management: Recent Advances". Frontiers in Medicine. 12 1597556. doi:10.3389/fmed.2025.1597556. PMC 12307495. PMID 40740956.
- ^ a b "First AI-designed drug, Rentosertib, officially named by USAN". Drug Target Review. March 14, 2025.
- ^ "Insilico Medicine Announces Developmental Candidate Benchmarks and Timelines for Novel Therapeutics Discovered Using Generative AI". EurekAlert! (American Association for the Advancement of Science). February 11, 2025.