zovegalisib

**Zovegalisib (RLY-2608)** is an investigational oral small molecule developed by Relay Therapeutics as the first allosteric, pan-mutant, and isoform-selective inhibitor of PI3Kα, targeting a cryptic pocket near the ATP-binding site to selectively inhibit mutant forms while sparing wild-type PI3Kα. This mechanism avoids common toxicities like hyperglycemia seen with orthosteric inhibitors such as alpelisib. It is primarily evaluated in combination with fulvestrant for PI3Kα-mutated, HR+/HER2- metastatic breast cancer in patients pretreated with CDK4/6 inhibitors and endocrine therapy, showing median PFS of 10.3 months overall (11.4 months in second-line), ORR of 39% (up to 60% in ESR1-mutant subgroup), and a favorable safety profile with low-grade, manageable adverse events. Phase 3 ReDiscover-2 trial is ongoing, with additional exploration in PI3Kα-driven vascular malformations.[1][2][3][4][7]

Other names

PI3Ka Inhibitor RLY-2608PI-3Ka Inhibitor RLY-2608PI 3Ka Inhibitor RLY-2608N-[(3R)-3-(2-chloro-5-fluorophenyl)-6-(5-cyano-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-oxo-2,3-dihydroisoindol-4-yl]-3-fluoro-5-(trifluoromethyl)benzamide