Journal of Medicinal Chemistry p. 9680 - 9696 (2015)
Update date:2022-08-15
Topics:
Marton, Zsuzsanna
Guillon, Rémi
Krimm, Isabelle
Preeti
Rahimova, Rahila
Egron, David
Jordheim, Lars P.
Aghajari, Nushin
Dumontet, Charles
Périgaud, Christian
Lionne, Corinne
Peyrottes, Suzanne
Chaloin, Laurent
We used a combined approach based on fragment-based drug design (FBDD) and in silico methods to design potential inhibitors of the cytosolic 5′-nucleotidase II (cN-II), which has been recognized as an important therapeutic target in hematological cancers. Two subgroups of small compounds (including adenine and biaryl moieties) were identified as cN-II binders and a fragment growing strategy guided by molecular docking was considered. Five compounds induced a strong inhibition of the 5′-nucleotidase activity in vitro, and the most potent ones were characterized as noncompetitive inhibitors. Biological evaluation in cancer cell lines showed synergic effect with selected anticancer drugs. Structural studies using X-ray crystallography lead to the identification of new binding sites for two derivatives and of a new crystal form showing important domain swapping. Altogether, the strategy developed herein allowed identifying new original noncompetitive inhibitors against cN-II that act in a synergistic manner with well-known antitumoral agents.
View MoreTIANJIN GST CHEMICAL TECHNOLOGY CO., LTD
Contact:+86-22-25210964
Address:Room. 208, No. -12-C, No. 13, Xinbei Road, Tanggu District, New Haixin Area, Tianjin City, China
Shanghai Goyic Pharmaceutical&Chemical Co,. Ltd
Contact:+86-021-60275964
Address:No. 528 ruiqing road
Improve Medical Technology(Nanxiong) Co., Ltd
Contact:86-751-3836997
Address:No.33, Pingan First Road, Fine Chemical Industry Base, Nanxiong City, Shaoguan, Guangdong, China
Contact:+86-0592 5353131
Address:No.56 Guani Road Software Park 2,Siming District
Huangshan Honghui Pharm Technology Co., Ltd.(expird)
website:http://www.honghuichem.com
Contact:18855958372
Address:Qingshan Wan No.1,Nanyuan Kou,SheXian Huangshan City,Anhui Province
Doi:10.1039/P29960002111
(1996)Doi:10.1139/v96-178
(1996)Doi:10.1016/0957-4166(96)00359-X
(1996)Doi:10.1021/jo961474c
(1996)Doi:10.1016/S0008-6215(00)86033-4
(1967)Doi:10.1016/0040-4039(96)01862-X
(1996)