Rentosertib

Rentosertib
INN: Rentosertib
Clinical data
Other namesISM001-055; INS018_055
Routes of
administration		Oral
Identifiers
  • [2,5′-Bi-1H-imidazole]-5-carboxamide, 4′-(4-fluorophenyl)-1′-(1-methylethyl)-N-[4-(4-methyl-1-piperazinyl)phenyl]
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
Chemical and physical data
FormulaC27H30FN7O
Molar mass487.583 g·mol−1
3D model (JSmol)
  • CC(C)N1C=NC(=C1C2=NC=C(N2)C(=O)NC3=CC=C(C=C3)N4CCN(CC4)C)C5=CC=C(C=C5)F
  • InChI=1S/C27H30FN7O/c1-18(2)35-17-30-24(19-4-6-20(28)7-5-19)25(35)26-29-16-23(32-26)27(36)31-21-8-10-22(11-9-21)34-14-12-33(3)13-15-34/h4-11,16-18H,12-15H2,1-3H3,(H,29,32)(H,31,36)
  • Key:ZVDNXHUSIKGTSF-UHFFFAOYSA-N

Rentosertib (also known as ISM001‑055 and INS018_055) is an investigational new drug that under evaluation for the treatment of idiopathic pulmonary fibrosis (IPF). It targets TNIK (TRAF2 and NCK-interacting protein kinase). It is asserted to be the first drug generated entirely by generative artificial intelligence to reach phase 3 human clinical trials, and the first to target a novel, AI-discovered biological pathway.

Development

Rentosertib was developed by Insilico Medicine using a generative AI platform designed to identify novel disease-associated targets and rapidly design optimized small-molecule inhibitors. 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.

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. The trial's primary endpoint was the incidence of treatment-emergent adverse events (TEAEs).

As of 2026, the drug was undergoing a phase 3 clinical trial.

In September 2026, the company published a study claiming that 6 independent proteomic ageing clocks all reported reduced biological age in the treatment arm of a phase 2a clinical trial. Separate pathway analyses "identified potential anti-aging shifts in senescence and metabolic processes".

Nomenclature

In March 2025, the United States Adopted Names (USAN) Council approved "Rentosertib" as the official nonproprietary name for ISM001-055.

References

  1. 1 2 3 4 5 6 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.
  2. 1 2 Field, Hayden (29 June 2023). "The first fully A.I.-generated drug enters clinical trials in human patients". CNBC.
  3. ↑ 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.
  4. ↑ 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.
  5. ↑ 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.
  6. 1 2 "First AI-designed drug, Rentosertib, officially named by USAN". Drug Target Review. March 14, 2025.
  7. ↑ "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.
  8. ↑ "Delving into the Latest Updates on Rentosertib with Synapse". synapse.patsnap.com. Retrieved 2026-09-07.
  9. ↑ Zhavoronkov, Alex; Galkin, Fedor; Chen, Shan; Ren, Feng; Aliper, Alex; Durymanov, Mikhail; Sidorenko, Denis; Cui, Hui; Han, Jing-Dong J.; Xu, Hao; Liu, Xiaodong; Xu, Zuojun; Kuppe, Christoph; Austin Argentieri, M.; Ying, Kejun (2026-09-07). "Integration of proteomic aging clocks in a phase 2a clinical trial supports simultaneous geroprotective assessment". Nature Biotechnology. Nature Publishing Group: 1–13. doi:10.1038/s41587-026-03286-y. ISSN 1546-1696.