146653-80-7Relevant articles and documents
Novel dual inhibitors targeting CDK4 and VEGFR2 synergistically suppressed cancer progression and angiogenesis
Huang, Zhi,Zhao,Qin, Zhongxiang,Li, Yongtao,Wang, Tianqi,Zhou, Wei,Zheng, Jianyu,Yang, Shengyong,Shi, Yi,Fan, Yan,Xiang, Rong
, (2019)
Based on the significantly synergistic effects of CDK4 and VEGFR2 inhibitors on growth of cancer cells, a series of novel multi-kinase inhibitors targeting CDK4 and VEGFR2 were designed, synthesized and evaluated, among which Roxyl-ZV-5J exhibited potent and balanced activities against both CDK4 and VEGFR2 with half-maximal inhibitory concentration at the nanomolar level. It effectively induced breast and cervical cancer cell cycle arrest and cell apoptosis. Roxyl-ZV-5J also inhibited the proliferation, tube formation and VEGFR2 downstream signaling pathways of HUVECs. Oral administration of Roxyl-ZV-5J led to significant tumor regression and anti-angiogenesis without obvious toxicity in SiHa xenograft mouse model. In addition, this compound showed good pharmacokinetics. This study confirmed a new tool for dual CDK-VEGFR2 pathways inhibition achieved with a single molecule, which provided valuable leads for further structural optimization and anti-angiogenesis and anti-tumor mechanism study.
Discovery of anilinopyrimidines as dual inhibitors of c-Met and VEGFR-2: Synthesis, SAR, and cellular activity
Zhan, Zhengsheng,Ai, Jing,Liu, Qiufeng,Ji, Yinchun,Chen, Tiantian,Xu, Yechun,Geng, Meiyu,Duan, Wenhu
supporting information, p. 673 - 678 (2014/07/07)
Both c-Met and VEGFR-2 are important targets for cancer therapies. Here we report a series of potent dual c-Met and VEGFR-2 inhibitors bearing an anilinopyrimidine scaffold. Two novel synthetic protocols were employed for rapid analoguing of the designed
