Scorpion Therapeutics reposted this
STX-721: EGFR Ex20ins Inhibitor with Potential Best-in-Class Selectivity | https://lnkd.in/dYSeJMXx STX-721 is an oral, covalent, mutant-selective inhibitor of EGFR and HER2 Exon 20 insertion (ex20ins) mutants, a well-validated target that saw its first approval with mobocertinib in 2022. Inhibition of wild-type (WT) EGFR is well-established to cause skin and gut toxicities, and selective inhibition of EGFR ex20ins mutants over WT may also allow greater efficacy to be seen at tolerated doses. On Oct. 10th, Scorpion Therapeutics announced that the first patient had been dosed with STX-721 in a Ph. I/II study for EGFR ex20ins mutant NSCLC (NCT06043817). This article highlights the discovery of STX-721 (presented by Ben Milgram, ACS San Francisco, 2023), an excellent case study in covalent drug discovery with respect to lead generation, warhead stability assessment, selectivity based on protein dynamics, and PK optimization of covalent compounds. Full article: https://lnkd.in/dYSeJMXx
