Li, Yongtao; Luo, Xiaohe; Guo, Qingxiang; Nie, Yongwei; Wang, Tianqi; Zhang, Chao; Huang, Zhi; Wang, Xin; Liu, Yanhua; Chen, Yanan; Zheng, Jianyu; Yang, Shengyong; Fan, Yan; Xiang, Rong published the artcile< Discovery of N1-(4-((7-Cyclopentyl-6-(dimethylcarbamoyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)phenyl)-N8-hydroxyoctanediamide as a Novel Inhibitor Targeting Cyclin-dependent Kinase 4/9 (CDK4/9) and Histone Deacetylase 1 (HDAC1) against Malignant Cancer>, Product Details of C10H15N3O2, the main research area is pyrrolopyrimidine preparation CDK4 CDK9 HDAC1 inhibitor treatment malignant cancer.
A series of highly potent, selective inhibitors targeting both CDK4/9 and HDAC1 have been designed and synthesized. N1-(4-((7-Cyclopentyl-6-(dimethylcarbamoyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)phenyl)-N8-hydroxyoctanediamide (I) was discovered. The lead compound I with excellent CDK4/9 and HDAC1 inhibitory activity of IC50 = 8.8, 12, and 2.2 nM, resp., can effectively induce apoptosis of cancer cell lines. The kinase profiling of compound I showed excellent selectivity and specificity. Compound I induces G2/M arrest in high concentration and G0/G1 arrest in low concentration to prevent the proliferation and differentiation of cancer cells. Mice bared-breast cancer treated with I showed significant antitumor efficacy. The insight into mechanisms of I indicated that it could induce cancer cell death via cell apoptosis based on CDK4/9 and HDAC1 repression and phosphorylation of p53. The data demonstrated the compound I could be a promising drug candidate for cancer therapy.
Journal of Medicinal Chemistry published new progress about Antitumor agents. 220731-04-4 belongs to class pyridine-derivatives, and the molecular formula is C10H15N3O2, Product Details of C10H15N3O2.