Journal of Medicinal Chemistry p. 4939 - 4952 (2007)
Update date:2022-08-04
Topics:
Parrish, Cynthia A.
Adams, Nicholas D.
Auger, Kurt R.
Burgess, Joelle L.
Carson, Jeffrey D.
Chaudhari, Amita M.
Copeland, Robert A.
Diamond, Melody A.
Donatelli, Carla A.
Duffy, Kevin J.
Faucette, Leo F.
Finer, Jeffrey T.
Huffman, William F.
Hugger, Erin D.
Jackson, Jeffrey R.
Knight, Steven D.
Luo, Lusong
Moore, Michael L.
Newlander, Ken A.
Ridgers, Lance H.
Sakowicz, Roman
Shaw, Antony N.
Sung, Chiu-Mei M.
Sutton, David
Wood, Kenneth W.
Zhang, Shu-Yun
Zimmerman, Michael N.
Dhanak, Dashyant
Kinesin spindle protein (KSP), an ATPase responsible for spindle pole separation during mitosis that is present only in proliferating cells, has become a novel and attractive anticancer target with potential for reduced side effects compared to currently available therapies. We report herein the discovery of the first known ATP-competitive inhibitors of KSP, which display a unique activity profile as compared to the known loop 5 (L5) allosteric KSP inhibitors that are currently under clinical evaluation. Optimization of this series led to the identification of biphenyl sulfamide 20, a potent KSP inhibitor with in vitro antiproliferative activity against human cells with either wild-type KSP (HCT116) or mutant KSP (HCT116 D 130V). In a murine xenograft model with HCT116 D130V tumors, 20 showed significant antitumor activity following intraperitoneal dosing, providing in vivo proof-of-principle of the efficacy of an ATP-competitive KSP inhibitor versus tumors that are resistant to the other known KSP inhibitors.
View MoreNINGBO PANGS CHEM INT’L CO., LTD.
Contact:+86-0574-27666801
Address:Floor 21, Building 11, Xintiandi, No. 689, Shijiroad, Ningbo, Zhejiang, China
Shaanxi King Stone Enterprise Company Limited
Contact:86-29-88353805,13609285751
Address:.209 Keji Road Hi-Tech industrial Develpment Zone .Xian China
Zibo Linzi Darong Fine Chemical Co., Ltd(expird)
Contact:86-532-67773200; 15689126900
Address:Qidu town,Linzi district,Zibo city,Shandong province,China
Shenzhen JYMed Technology Co.,Ltd.
website:http://www.jymedtech.com
Contact:+86-755-26612112
Address:1#8,9/F, Biomedicine innovation Industrial Park, No.14, Jinhui Road, Pingshan Sistrict, Shenzhen, China
Changzhou LanXu Chemical Co.,ltd.(expird)
Contact:86-0519-86330911,13656129734,15261186386
Address:Room 524, Depart.Chemical, Changzhou Science and Eductaion town, Jiangsu, China;Factory: Haian Fine Chemical Industry Park,Nantong,Jiangsu,China
Doi:10.1246/bcsj.59.2421
(1986)Doi:10.1039/c9ob02676b
(2020)Doi:10.1016/S0040-4020(01)87377-4
(1986)Doi:10.1021/jo00391a006
(1987)Doi:10.1055/s-1986-31752
(1986)Doi:10.1021/jo01060a053
(1961)