作者: Luo, Guolong ; Wu, Tianbang ; Shen, Hui ; Zhang, Cheng ; Zhuang, Xiaoxi ; Liu, Jinsong ; Wang, Chao ; Kong, Xiangqian ; Hu, Qingqing ; Hu, Jiankang ; Xiang, Qiuping ; Xu, Yong ; Zhang, Yan ; Zou, Lingjiao ; Wu, Xishan

CREB (cyclic-AMP responsive element binding protein) binding protein (CBP) is a potential target for prostate cancer treatment. Herein, we report the structural optimization of a series of 1-(indolizin-3-yl)ethan-1-one compounds as new selective CBP bromodomain inhibitors, aiming to improve cellular potency and metabolic stability. This process led to compound 9g (Y08284), which possesses good liver microsomal stability and pharmacokinetic properties (F = 25.9%). Furthermore, the compound is able to inhibit CBP bromodomain as well as the proliferation, colony formation, and migration of prostate cancer cells. Additionally, the new inhibitor shows promising antitumor efficacy in a 22Rv1 xenograft model (TGI = 88%). This study provides new lead compounds for further development of drugs for the treatment of prostate cancer.

2005-11-01·Doklady Biological Sciences

Speciation in the Yeast Lachancea thermotolerans: Molecular Genetic Evidence

Article

作者: E. V. Serpova ; E. S. Naumova ; G. I. Naumov

This study aims to characterize the Mel⁺ strains that was unusual for L. thermotolerans, as well as some Mel^- strains isolated in Far East, Finland, and the Crimea.According to the data, a population represented by a type culture and a second, genetically divergent, melibiose-utilizing yeast population belong to this species.There are two genetic groups of Lachancea thermotolerans strains, the first one includes the type strain NRRL Y-8284 and the strains incapable of melibiose utilizing as a rule.The second species consists of melibiose-utilizing strains.Both species are cosmopolitan, because they are encountered in different parts of the world.The population structure of yeast L. thermotolerans represents an interesting model for studying the ecol. genetic mechanisms of inter- and intraspecific differentiation.

100 项与 Y08284 相关的药物交易

登录后查看更多信息