AZD4625 is a Potent and Selective Inhibitor of KRASG12C

  • Mol Cancer Ther. 2022 Oct 7;21(10):1535-1546. doi: 10.1158/1535-7163.MCT-22-0241.
Atanu Chakraborty  #  1 ,  Lyndsey Hanson  #  1 ,  David Robinson  #  1 ,  Hilary Lewis  1 ,  Sue Bickerton  1 ,  Michael Davies  1 ,  Radoslaw Polanski  1 ,  Rebecca Whiteley  1 ,  Alex Koers  1 ,  James Atkinson  1 ,  Tamara Baker  1 ,  Ivan Del Barco Barrantes  1 ,  Giovanni Ciotta  1 ,  Jason G Kettle  1 ,  Lukasz Magiera  1 ,  Carla P Martins  1 ,  Alison Peter  1 ,  Eleanor Wigmore  1 ,  Zoe Underwood  1 ,  Sabina Cosulich  1 ,  Michael Niedbala  2 ,  Sarah Ross  1
Affiliations
  • 1. AstraZeneca, Cambridge, United Kingdom.
  • 2. AstraZeneca, Waltham, Massachusetts.
  • # Contributed equally.
PMID: 35930755 DOI: 10.1158/1535-7163.MCT-22-0241
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.

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