molecules of the month

Context. “Compound 57”  (Roche) is an oral allosteric EGFRL858R inhibitor being developed for NSCLC. Drug resistance and associated disease relapse continue to remain unmet needs for patients with NSCLC tumors harboring EGFR mutations, despite the availability of three generations of TKIs for EGFR+ NSCLC. Although the widely used third-generation agent osimertinib has been highly effective against the commonly occurring T790M mutation, the exon 19 deletion (ex19del), and the L858R sensitizing mutations, the drug has been largely inactive against the C797S-acquired mutation. Consequently, fourth-generation TKIs interact with an allosteric site generated by the L858R mutation, unlike current generation ATP-competitive agents. The newest class of inhibitors are actively been explored for treatment of L858R/C797-, L858R/T790M-, or L858R/T790M/C797S-mutant EGFR. We previously highlighted JBJ-09-063…