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AZD4625 is a Potent and Selective Inhibitor of KRASG12C.

ABSTRACT: AZD4625 is a potent, selective, and orally bioavailable inhibitor of oncogenic KRASG12C as demonstrated in cellular assays and in vivo in preclinical cell line-derived and patient-derived xenograft models. In vitro and cellular assays have shown selective binding and inhibition of the KRASG12C mutant isoform, which carries a glycine to cysteine mutation at residue 12, with no binding and inhibition of wild-type RAS or isoforms carrying non-KRASG12C mutations. The pharmacology of AZD4625 shows that it has the potential to provide therapeutic benefit to patients with KRASG12C mutant cancer as either a monotherapy treatment or in combination with other targeted drug agents.

SUBMITTER: Chakraborty A

PROVIDER: S-EPMC9538594 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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AZD4625 is a Potent and Selective Inhibitor of KRASG12C.

Chakraborty Atanu A Hanson Lyndsey L Robinson David D Lewis Hilary H Bickerton Sue S Davies Michael M Polanski Radoslaw R Whiteley Rebecca R Koers Alex A Atkinson James J Baker Tamara T Del Barco Barrantes Ivan I Ciotta Giovanni G Kettle Jason G JG Magiera Lukasz L Martins Carla P CP Peter Alison A Wigmore Eleanor E Underwood Zoe Z Cosulich Sabina S Niedbala Michael M Ross Sarah S

Molecular cancer therapeutics 20221001 10

AZD4625 is a potent, selective, and orally bioavailable inhibitor of oncogenic KRASG12C as demonstrated in cellular assays and in vivo in preclinical cell line-derived and patient-derived xenograft models. In vitro and cellular assays have shown selective binding and inhibition of the KRASG12C mutant isoform, which carries a glycine to cysteine mutation at residue 12, with no binding and inhibition of wild-type RAS or isoforms carrying non-KRASG12C mutations. The pharmacology of AZD4625 shows th ...[more]

PMID: 35930755

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