Bond MJ,
Chu L,
Nalawansha DA,
Li K,
Crews CM.
*
Yale University, New Haven, USA
Targeted Degradation of Oncogenic KRASG12C by VHL-Recruiting PROTACs.
ACS Cent. Sci. 2020;
6: 1367-1375
DOI:
10.1021/acscentsci.0c00411
Key words
KRAS - targeted degradation - cancer - drug development
Significance
KRas is one of the most promising cancer drug targets, but targeting it has been a challenge. Crews and co-workers employed covalent KRas G12C inhibitors for the development of PROTACS that allowed for its targeted degradation.
Comment
A solvent-exposed site in the clinical drug candidate MRTX849 was identified and used for conjugation to a linker and a VHL ligand to yield the PROTAC LC-2.
