D-1553: A novel KRAS^G12C inhibitor with potent and selective cellular and in vivo antitumor activity.

ABSTRACT: D-1553 is a small molecule inhibitor selectively targeting KRAS^G12C and currently in phase II clinical trials. Here, we report the preclinical data demonstrating antitumor activity of D-1553. Potency and specificity of D-1553 in inhibiting GDP-bound KRAS^G12C mutation were determined by thermal shift assay and KRAS^G12C -coupled nucleotide exchange assay. In vitro and in vivo antitumor activity of D-1553 alone or in combination with other therapies were evaluated in KRAS^G12C mutated cancer cells and xenograft models. D-1553 showed selective and potent activity against mutated GDP-bound KRAS^G12C protein. D-1553 selectively inhibited ERK phosphorylation in NCI-H358 cells harboring KRAS^G12C mutation. Compared to the KRAS WT and K

SUBMITTER: Shi Z 

PROVIDER: S-EPMC10323112 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature