Department of Medicinal Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China; Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China.
Division of Antitumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203, China.
Bioorg Med Chem Lett. 2021 Feb 1;33:127749. doi: 10.1016/j.bmcl.2020.127749. Epub 2020 Dec 24.
In an in-house screening, 1H-pyrrolo[2,3-b]pyridine scaffold was found to have high inhibition on TNIK. Several series of compounds were designed and synthesized, among which some compounds had potent TNIK inhibition with IC values lower than 1 nM. Some compounds showed concentration-dependent characteristics of IL-2 inhibition. These results provided new applications of TNIK inhibitors and new prospects of TNIK as a drug target.
在内部筛选中，发现 1H-吡咯并[2,3-b]吡啶支架对 TNIK 具有高抑制性。设计并合成了几个系列的化合物，其中一些化合物对 TNIK 的抑制作用很强，IC 值低于 1nM。一些化合物表现出与浓度相关的 IL-2 抑制特征。这些结果为 TNIK 抑制剂提供了新的应用，也为 TNIK 作为药物靶点提供了新的前景。
