Evidence mapPaperPMID 40461817Full record

Trial reportNature medicine2025

A generative AI-discovered TNIK inhibitor for idiopathic pulmonary fibrosis: a randomized phase 2a trial.

Zuojun Xu, Feng Ren, Ping Wang, Jie Cao, Chunting Tan, Dedong Ma, Li Zhao, Jinghong Dai, Yipeng Ding, Haohui Fang and 17 more

Abstract readRandomized Controlled TrialClinical Trial, Phase IIMulticenter Study
In one paragraph

Trial report in Nature medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed, 1 pooled it
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

58 citing papers in PubMed, 1 synthesis or guideline pooled it.

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  15. Hallmarks of the ageing lung: 10 years later.The European respiratory journal · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

27 authors.

Zuojun XuDepartment of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Beijing, China. xuzj@hotmail.com.ORCID http://orcid.org/0000-0001-9659-6993
Feng RenInsilico Medicine Shanghai, Shanghai, China.ORCID http://orcid.org/0000-0001-9157-9182
Ping WangDepartment of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Beijing, China.
Jie CaoDepartment of Respiratory and Critical Care Medicine, Tianjin Medical University General Hospital, Tianjin, China.
Chunting TanDepartment of Pulmonary and Critical Care Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Dedong MaDepartment of Respiratory Disease, Qilu Hospital of Shandong University, Jinan, China.
Li ZhaoDepartment of Respiratory Medicine, Shengjing Hospital of China Medical University, Shenyang, China.
Jinghong DaiDepartment of Pulmonary and Critical Care Medicine, Nanjing Drum Tower Hospital, Nanjing University, Nanjing, China.
Yipeng DingDepartment of Respiratory and Critical Care Medicine, Hainan General Hospital, Haikou, China.
Haohui FangDepartment of Respiratory and Critical Care, Anhui Chest Hospital, Hefei, China.
Huiping LiDepartment of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University, Shanghai, China.ORCID http://orcid.org/0000-0002-6998-9828
Hong LiuDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Fengming LuoDepartment of Pulmonary and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, China.
Ying MengDepartment of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Pinhua PanDepartment of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, China.
Pingchao XiangDepartment of Respiratory and Critical Care Medicine, Peking University Shougang Hospital, Beijing, China.
Zuke XiaoDepartment of Respiratory and Critical Care Medicine, Jiangxi Provincial People's Hospital, Nanchang, China.
Sujata RaoInsilico Medicine US, Cambridge, MA, USA.
Carol SatlerInsilico Medicine US, Cambridge, MA, USA.
Sang LiuInsilico Medicine Shanghai, Shanghai, China.
Yuan LvInsilico Medicine Shanghai, Shanghai, China.
Heng ZhaoInsilico Medicine Shanghai, Shanghai, China.
Shan ChenInsilico Medicine Shanghai, Shanghai, China.
Hui CuiInsilico Medicine Shanghai, Shanghai, China.
Mikhail KorzinkinInsilico Medicine AI, Abu Dhabi, United Arab Emirates.
David GennertInsilico Medicine US, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-8668-3601
Alex ZhavoronkovInsilico Medicine Shanghai, Shanghai, China. alex@insilico.com.ORCID http://orcid.org/0000-0001-7067-8966

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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 rentosertib QD (n = 18) or placebo (n = 17). The primary endpoint was the percentage of patients who have at least one treatment-emergent adverse event, which was similar across all treatment arms (72.2% in patients receiving 30 mg rentosertib QD (n = 13/18), 83.3% for 30 mg rentosertib BID (n = 15/18), 83.3% for 60 mg rentosertib QD (n = 15/18) and 70.6% for placebo (n = 12/17)). Treatment-related serious adverse event rates were low and comparable across treatment groups, with the most common events leading to treatment discontinuation related to liver toxicity or diarrhea. Secondary endpoints included pharmacokinetic dynamics (C

Indexed as

Artificial IntelligenceIdiopathic Pulmonary FibrosisAgedDouble-Blind MethodFemaleHumansMaleMiddle AgedTreatment Outcome

Identifiers

PMID40461817
PMCPMC12353801

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.