PROTAC CDK2/4/6 Degrader-2 is a CDK2/4/6 PROTAC degrader. PROTAC CDK2/4/6 Degrader-2. PROTAC CDK2/4/6 Degrader-2 can be converted into the prodrug PROTAC CDK2/4/6 Degrader-1 through a one-step reaction with chloromethyl pivalate. PROTAC CDK2/4/6 Degrader-2 degrades CDK2/4/6 and their complex in malignant melanomas cells. PROTAC CDK2/4/6 Degrader-2 induces cell cycle arrest and cell apoptosis in various cancer cells, in particular for melanomas. PROTAC CDK2/4/6 Degrader-2 can be used for malignant melanomas research [1]. (Pink: CDK2 and CDK4 and CDK6 ligand; Blue: Cereblon ligand; Black: linker).
In Vitro, PROTAC CDK2/4/6 Degrader-2 (compound 3) (72 h) exhibits prominent anti-proliferative activity against B16F10 and A375, with IC50s of 0.09861 and 0.1659 μM, respectively[1]. PROTAC CDK2/4/6 Degrader-2 (0-2000 nM, 0-12 h) mediates CDK2/4/6 protein degradation and impairs downstream Rb signaling activation by hijacking the E3 ubiquitin ligase CRBN in B16F10 and A375 cells[1]. PROTAC CDK2/4/6 Degrader-2 (50-500 nM, 7 days) exerts significant anti-proliferative activity in B16F10 and A375 cells[1]. PROTAC CDK2/4/6 Degrader-2 (125-1000 nM,48 h) significantly induces apoptosis of A375 and B16F10 cells in a dose-dependent manner in B16F10 and A375 cells[1]. PROTAC CDK2/4/6 Degrader-2 (0-2000 nM, 48 h) induces caspase-dependent apoptosis via the common P53/Bcl-2/Bax apoptotic pathway in B16F10 and A375 cells[1]. PROTAC CDK2/4/6 Degrader-2 (25-1000 nM,48 h) induces cell cycle arrest via the degradation of cell cycle-related proteins CDK2/4/6 in A375 and B16F10 cells[1].
References:
[1]. Wei M, et al. First orally bioavailable prodrug of proteolysis targeting chimera (PROTAC) degrades cyclin-dependent kinases 2/4/6 in vivo. Eur J Med Chem. 2021 Jan 1;209:112903.
In Vitro, PROTAC CDK2/4/6 Degrader-2 (compound 3) (72 h) exhibits prominent anti-proliferative activity against B16F10 and A375, with IC50s of 0.09861 and 0.1659 μM, respectively[1]. PROTAC CDK2/4/6 Degrader-2 (0-2000 nM, 0-12 h) mediates CDK2/4/6 protein degradation and impairs downstream Rb signaling activation by hijacking the E3 ubiquitin ligase CRBN in B16F10 and A375 cells[1]. PROTAC CDK2/4/6 Degrader-2 (50-500 nM, 7 days) exerts significant anti-proliferative activity in B16F10 and A375 cells[1]. PROTAC CDK2/4/6 Degrader-2 (125-1000 nM,48 h) significantly induces apoptosis of A375 and B16F10 cells in a dose-dependent manner in B16F10 and A375 cells[1]. PROTAC CDK2/4/6 Degrader-2 (0-2000 nM, 48 h) induces caspase-dependent apoptosis via the common P53/Bcl-2/Bax apoptotic pathway in B16F10 and A375 cells[1]. PROTAC CDK2/4/6 Degrader-2 (25-1000 nM,48 h) induces cell cycle arrest via the degradation of cell cycle-related proteins CDK2/4/6 in A375 and B16F10 cells[1].
References:
[1]. Wei M, et al. First orally bioavailable prodrug of proteolysis targeting chimera (PROTAC) degrades cyclin-dependent kinases 2/4/6 in vivo. Eur J Med Chem. 2021 Jan 1;209:112903.