molecules of the month


oral KRAS(G12C) inhibitor

oral efficacy in xenograft model

from literature starting point and SBDD

J. Med. Chem.

AstraZeneca, Cambridge, UK

AZD4625 chemical structure, oral KRAS(G12C) inhibitor - AstraZeneca, Cambridge, UK
4 mins read

Context. AZD4625 (AstraZeneca) is an oral inhibitor of KRASG12C being developed for the treatment of advanced solid malignancies. As indicated for JDQ443, the KRASG12C mutation presents the perfect “Achilles heel” for targeting a KRAS protein previously thought undruggable. The protein is a current hot topic in precision oncology, with Amgen’s first-in-class sotorasib (Lumakras) having been approved, Mirati's adagrasib nearing approval, and other key agents such as Genetech’s GDC-6036, Eli Lilly’s LY3537982, InvestisBio’s D-1553, and Boehringer Ingelheim’s BI 1823911 all currently in early clinical development. AZD4625 is unique chemically, as it lacks a basic amine moiety that is typically carried by other KRASG12C inhibitors, potentially exhibiting novel properties different from existing compounds. AZD4625 has not entered clinical evaluation though a Ph.…

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