Activin receptor‑like kinase-5 (ALK5) is an outstanding member of the transforming growth factor-β (TGF-β) family. (TGF-β) signaling pathway integrates pleiotropic proteins that regulate various cellular processes such as growth, proliferation, and differentiation. Dysregulation within the signaling pathway can cause variety of diseases, such as fibrosis, cardiovascular disease, and especially cancer, rendering ALK5 a potential drug target. Hence, various small molecules have been designed and synthesized as potent ALK5 inhibitors. In this review, we shed light on the current ATP-competitive inhibitors of ALK5 through diverse heterocyclic based scaffolds that are in clinical or pre-clinical phases of development. Moreover, we focused on the binding interactions of the compounds to the ATP binding site and the structure–activity relationship (SAR) of each scaffold, revealing new scopes for designing novel candidates with enhanced selectivity and metabolic profiles.

中文翻译：

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激活素受体样激酶 5 (ALK5) 抑制剂的发现进展

激活素受体样激酶 5 (ALK5) 是转化生长因子 -β (TGF-β) 家族的杰出成员。 (TGF-β) 信号通路整合了调节各种细胞过程（如生长、增殖和分化）的多效性蛋白。信号通路内的失调可导致多种疾病，如纤维化、心血管疾病，尤其是癌症，这使得 ALK5 成为潜在的药物靶点。因此，各种小分子被设计和合成为有效的 ALK5 抑制剂。在这篇综述中，我们通过处于临床或临床前开发阶段的各种基于杂环的支架，阐明了当前 ALK5 的 ATP 竞争性抑制剂。此外，我们重点关注化合物与 ATP 结合位点的结合相互作用以及每个支架的构效关系 (SAR)，揭示了设计具有增强选择性和代谢特征的新型候选物的新范围。