A small-molecule TNIK inhibitor targets fibrosis in preclinical and clinical models
Problem
Idiopathic pulmonary fibrosis is an aggressive, high-mortality lung disease where putative drug targets have failed to translate into effective clinical therapies.
Why it matters
IPF has high mortality and no effective clinical therapy, creating urgent unmet medical need.
What the AI did
A predictive AI approach identified TNIK as an anti-fibrotic target, and AI-driven methodology generated INS018_055, a small-molecule TNIK inhibitor with drug-like properties.
Results
Anti-fibrotic and anti-inflammatory activity across organs in vivo; safety, tolerability and pharmacokinetics validated in a randomized, double-blinded, placebo-controlled phase I trial (NCT05154240, 78 healthy participants) and a comparable China phase I trial (CTR20221542).
Impact
Peer-reviewed in Nature Biotechnology, with clinical validation so far limited to phase I safety and tolerability.
Record
| Venue | Nature Biotechnology |
|---|---|
| Published | 2024 |
| Work type | article |
| Authors | Feng Ren, Alex Aliper, Jian Chen, Heng Zhao, Sujata Rao, Christoph Kuppe, Ivan V. Ozerov, Man Zhang et al. |
| Citations | 330 (OpenAlex, at import time) |
| References | 94 |
| Model or method | not stated in source |
| Organization | not stated in source |
| Primary source | https://doi.org/10.1038/s41587-024-02143-0 |
| Open access | hybrid |
| Keywords | TNIK inhibitor, INS018_055, idiopathic pulmonary fibrosis, AI drug discovery, phase I trial |
Importance rating
significant — thousands to millions affected
Abstract states IPF is aggressive with a high mortality rate and that putative targets have failed to translate into effective therapies, indicating urgent unmet medical need; no patient counts given.