Abstract：
TGF-β is an immunosuppressive cytokine and plays a key role in progression of cancer by inducing immunosuppression in tumor microenvironment. Therefore, inhibition of TGF-β signaling pathway may provide a potential therapeutic intervention in treating cancers. Herein, we report the discovery of a series of novel thiazole derivatives as potent inhibitors of ALK5, a serine-threonine kinase which is responsible for TGF-β signal transduction. Compound 29b was identified as a potent inhibitor of ALK5 with an IC50 value of 3.7 nM with an excellent kinase selectivity.
摘要：
TGF-β是一种免疫抑制细胞因子，通过在肿瘤微环境中诱导免疫抑制在癌症的进展中起关键作用。因此,TGF-β信号通路的抑制可能为治疗癌症提供潜在的治疗干预。在这里，我们报道了一系列新型噻唑衍生物作为ALK5的有效抑制剂的发现，ALK5是一种负责TGF-β信号转导的丝氨酸-苏氨酸激酶。化合物29b被鉴定为ALK5的有效抑制剂,IC50值为3.7nM,具有优异的激酶选择性。
