INY-03-041 is a potent, highly selective and PROTAC-based pan- AKT degrader consisting of the ATP-competitive AKT inhibitor Ipatasertib conjugated to Lenalidomide . INY-03-041 inhibits AKT1 , AKT2 and AKT3 with IC 50 s of 2.0, 6.8 and 3.5 nM, respectively In Vitro INY-03-041 (10-1000 nM; 0-24 hours) induces potent degradation of all three AKT isoforms in MDA-MB-468 cells. INY-03-041 exhibits potent in vitro inhibition of S6K1 (IC 50 =37.3 nM) and PKG1 (IC 50 = 33.2 nM). INY-03-041 displays enhanced anti-proliferative effects compared with Ipatasertib in MDA-MB-468 and HCC1937 cells. INY-03-041 (250 nM, 12 h) promotes sustained AKT degradation and inhibition of downstream signaling effects for up to 96 h, even after compound washout. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Western Blot AnalysisCell Line: MDA-MB-468 cells Concentration: 10 nM, 50 nM, 100 nM, 250 nM, 500 nM, 1000 nM Incubation Time: 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours Result: Induced potent degradation of all three AKT isoforms in a dose-dependent manner after a 12-h treatment, with maximal degradation observed between 100 and 250 nM. At concentrations of 500 nM and greater, AKT degradation is diminished. Treatment with 250 nM of INY-03-041 over time reveals partial degradation of all AKT isoforms within 4 h and progressive loss of AKT abundance out to 24 h. Form:Solid IC50& Target:Akt1 2.0 nM (IC 50 ) Akt3 3.5 nM (IC 50 ) Akt2 6.8 nM (IC 50 ) Cereblon