biostudies-literatureUnknown31(8)Xu ZDespite substantial progress in artificial intelligence (AI) for generative chemistry, few novel AI-discovered or AI-designed drugs have reached human clinical trials. Here we present the results of the first phase 2a multicenter, double-blind, randomized, placebo-controlled trial testing the safety and efficacy of rentosertib (formerly ISM001-055), a first-in-class AI-generated small-molecule inhibitor of TNIK, a first-in-class target in idiopathic pulmonary fibrosis (IPF) discovered using generative AI. IPF is an age-related progressive lung condition with no current therapies available that reverse the degenerative course of disease. Patients were randomized to 12 weeks of treatment with 30 mg rentosertib once daily (QD, n = 18), 30 mg rentosertib twice daily (BID, n = 18), 60 mg rentosNature medicine2602-2610https://www.ebi.ac.uk/biostudies/studies/S-EPMC12353801biostudies-literatureA generative AI-discovered TNIK inhibitor for idiopathic pulmonary fibrosis: a randomized phase 2a trial.PMC12353801Liu HFang HXiang PRao SCao JLv YLiu SMeng YRen FWang PZhao LDing YCui HChen SZhavoronkov AZhao HLi HXiao ZSatler CTan CLuo FKorzinkin MGennert DPan PMa DDai JXu ZfalseA generative AI-discovered TNIK inhibitor for idiopathic pulmonary fibrosis: a randomized phase 2a trial.Despite substantial progress in artificial intelligence (AI) for generative chemistry, few novel AI-discovered or AI-designed drugs have reached human clinical trials. Here we present the results of the first phase 2a multicenter, double-blind, randomized, placebo-controlled trial testing the safety and efficacy of rentosertib (formerly ISM001-055), a first-in-class AI-generated small-molecule inhibitor of TNIK, a first-in-class target in idiopathic pulmonary fibrosis (IPF) discovered using generative AI. IPF is an age-related progressive lung condition with no current therapies available that reverse the degenerative course of disease. Patients were randomized to 12 weeks of treatment with 30 mg rentosertib once daily (QD, n = 18), 30 mg rentosertib twice daily (BID, n = 18), 60 mg rentos2025-01-01T00:00:00Z2025 Aug2026-07-15T06:30:51.267Z2026-06-30T03:23:41.839ZS-EPMC123538014046181710.1038/s41591-025-03743-2