Zhang, Hefeng; Peng, Xia; Dai, Yang; Shao, Jingwei; Ji, Yinchun; Sun, Yiming; Liu, Bo; Cheng, Xu; Ai, Jing; Duan, Wenhu published the artcile< Discovery of a Pyrimidinedione Derivative as a Potent and Orally Bioavailable Axl Inhibitor>, Quality Control of 1046832-21-6, the main research area is pyrimidinedione preparation receptor tyrosine kinase anticancer pharmacokinetic mol modeling.
The receptor tyrosine kinase Axl plays important roles in promoting cancer progression, metastasis, and drug resistance and has been identified as a promising target for anticancer therapeutics. We used mol. modeling-assisted structural optimization starting with the low micromolar potency compound I to discover compound II, a highly potent and orally bioavailable Axl inhibitor. Selectivity profiling showed that II could inhibit the well-known oncogenic kinase Met with equal potency to its inhibition of Axl superfamily kinases. Compound II significantly inhibited cellular Axl and Met signaling, suppressed Axl- and Met-driven cell proliferation, and restrained Gas6/Axl-mediated cancer cell migration or invasion. Furthermore, II exhibited significant antitumor efficacy in Axl-driven and Met-driven tumor xenograft models, causing tumor stasis or regression at well-tolerated doses. All these favorable data make II a promising therapeutic candidate for cancer treatment.
Journal of Medicinal Chemistry published new progress about Antitumor agents. 1046832-21-6 belongs to class pyrazoles-derivatives, and the molecular formula is C11H19BN2O2, Quality Control of 1046832-21-6.
Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics