Description
SIM1 is a potent von Hippel-Lindau (VHL)-based trivalent PROTAC capable of degradation for all BET family members, with preference for BRD2 degradation ( IC 50 =1.1 nM; Kd =186 nM). SIM1 shows sustained anti-cancer activityIn VitroSIM1 (1 nM; 30 hours; MV4-11 cells) results in measurable cellular death after 6 hours. SIM1 (1 µM; 4 hours; HEK293 cells) degrades BET proteins. SIM1 induces conformational changes upon binding to the BET protein to simultaneously engage with high avidity both its bromodomains in a cis intramolecular fashion. SIM1 engages BD1 and BD2 intramolecularly and forms a 1:1:1 ternary complex with VHL and BRD4. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Viability AssayCell Line: MV4-11 cells Concentration: 1 nM Incubation Time: 30 hours Result: Resulted in measurable cellular death after 6 hours. Western Blot AnalysisCell Line: HEK293 cells Concentration: 1 µM Incubation Time: 4 hours Result: Degraded BET proteins.Form:SolidIC50& Target:BRD2 1.1 nM (IC 50 ) BRD2 186 nM (Kd) BRD3 BRD4