Angewandte Chemie - International Edition p. 199 - 204 (2014)
Update date:2022-08-11
Topics:
Lim, Sang Min
Westover, Kenneth D.
Ficarro, Scott B.
Harrison, Rane A.
Choi, Hwan Geun
Pacold, Michael E.
Carrasco, Martin
Hunter, John
Kim, Nam Doo
Xie, Ting
Sim, Taebo
Jaenne, Pasi A.
Meyerson, Matthew
Marto, Jarrod A.
Engen, John R.
Gray, Nathanael S.
We report the synthesis of a GDP analogue, SML-8-73-1, and a prodrug derivative, SML-10-70-1, which are selective, direct-acting covalent inhibitors of the K-Ras G12C mutant relative to wild-type Ras. Biochemical and biophysical measurements suggest that modification of K-Ras with SML-8-73-1 renders the protein in an inactive state. These first-in-class covalent K-Ras inhibitors demonstrate that irreversible targeting of the K-Ras guanine-nucleotide binding site is potentially a viable therapeutic strategy for inhibition of Ras signaling. Putting a stop to Ras: Two new selective, direct-acting covalent inhibitors of the K-Ras G12C mutant are reported. Studies suggest that the modification of K-Ras with SML-8-73-1 renders the protein inactive. These novel covalent inhibitors demonstrate that irreversible targeting of the K-Ras guanine-nucleotide binding site is potentially a viable therapeutic strategy for inhibition of Ras signaling. Copyright
View MoreJiaxing Trustworthy Import And Export Co.,Ltd
Contact:+86-573-82030555
Address:Room 1202, Unit B, Charming plaza,No.1558 East Zhongshan Road , Jiaxing City, Zhejiang Province, China.
Xiamen XM-Innovation Chemical Co., Ltd
Contact:+86-592-3216205
Address:Unit Q, 11/F, No.1 Office Building, Wuyuan Bay Business Center, Huli District, Xiamen City, Fujian Province, P.R.C
Chongqing Changfeng Chemical Co., Ltd.
website:http://www.changfengchem.com
Contact:+86-23-67896333
Address:30th Floor, Longhu Ziduxingzuo Building A, 1st Branch,YuSong Rd., Yubei District, Chongqing, China
Xi'an North Information Industry Co., Ltd. Weilv Chemical Department
Contact:+86-29-88156413
Address:Jixiang Road 99 Xi'an Shaanxi Province
Shanghai Yuanding Chem. Sci. & Tech. Co., Ltd.
website:http://www.shydtec.com
Contact:86-21-57721279
Address:Science and Technology Park, Songjiang District, Shanghai, China
Doi:10.1021/ja01650a033
(1954)Doi:10.1002/anie.200806276
(2009)Doi:10.1039/a909703a
(2000)Doi:10.1007/s10562-010-0448-3
(2011)Doi:10.1021/jo00118a006
(1995)Doi:10.1016/S0040-4039(97)01036-8
(1997)