A small-molecule TNIK inhibitor targets fibrosis in preclinical and clinical models.
特发性肺纤维化（IPF）是一种侵袭性间质性肺病，死亡率高，既往候选药物靶点未能在临床转化为有效疗法。研究利用预测性人工智能方法识别TRAF2和NCK相互作用激酶（TNIK）为抗纤维化靶点，并据此生成小分子TNIK抑制剂INS018_055。该化合物具有良好成药性，经口服、吸入或局部给药在体内多器官显示抗纤维化活性，并在多项体内研究中验证了抗炎作用。一项随机、双盲、安慰剂对照I期临床试验（NCT05154240）纳入78名健康受试者，验证了其安全性、耐受性和药代动力学；中国另一项I期试验（CTR20221542）也显示可比的安全性和药代动力学特征。从靶点发现到临床前候选药物提名约历时18个月，展示了生成式AI驱动药物发现流程的能力。
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完整作者
Feng Ren、Alex Aliper、Jian Chen、Heng Zhao、Sujata Rao、Christoph Kuppe、Ivan V Ozerov、Man Zhang、Klaus Witte、Chris Kruse、Vladimir Aladinskiy、Yan Ivanenkov、Daniil Polykovskiy、Yanyun Fu、Eugene Babin、Junwen Qiao、Xing Liang、Zhenzhen Mou、Hui Wang、Frank W Pun、Pedro Torres-Ayuso、Alexander Veviorskiy、Dandan Song、Sang Liu、Bei Zhang、Vladimir Naumov、Xiaoqiang Ding、Andrey Kukharenko、Evgeny Izumchenko、Alex Zhavoronkov
作者机构
- Insilico Medicine Shanghai Ltd., Shanghai, China.
- Insilico Medicine AI Limited, Abu Dhabi, UAE.
- Insilico Medicine Hong Kong Ltd., Hong Kong Science and Technology Park, Hong Kong SAR, China.
- Department of Clinical Pharmacology, Affiliated Xiaoshan Hospital, Hangzhou Normal University, Hangzhou, China.
- Insilico Medicine US Inc., New York, NY, USA.
- Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Aachen, Germany.
- Department of Nephrology, University Clinic RWTH Aachen, Aachen, Germany.
- Insilico Medicine Canada Inc, Montreal, Quebec, Canada.
- Department of Cancer and Cellular Biology, Lewis Katz School of Medicine, Temple University, PA, USA.
- Division of Nephrology, Zhongshan Hospital Shanghai Medical College, Fudan University, Shanghai, China.
- Section of Hematology and Oncology, Department of Medicine, University of Chicago, Chicago, IL, USA.
- Insilico Medicine AI Limited, Abu Dhabi, UAE. alex@insilico.com.
- Insilico Medicine Hong Kong Ltd., Hong Kong Science and Technology Park, Hong Kong SAR, China. alex@insilico.com.
- Insilico Medicine US Inc., New York, NY, USA. alex@insilico.com.
- Insilico Medicine Canada Inc, Montreal, Quebec, Canada. alex@insilico.com.
技术路线
AI预测靶点→AI驱动生成小分子INS018_055→体内外抗纤维化/抗炎活性评估→随机双盲安慰剂对照I期临床试验（NCT05154240，78名健康受试者）安全性/耐受性/药代动力学验证→中国I期试验（CTR20221542）验证安全性/药代动力学
最近 5 个完整年度引用趋势
不含 2026 年，仅展示最近 5 个完整年度。
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