PROTAC B-Raf degrader 1 (compound 2) is a proteolysis targeting chimera (PROTAC) for the degradation of B-Raf based on Cereblon ligand with anti-cancer activity
In Vitro
The IC 50 values of PROTAC B-Raf degrader 1 (compound 2) towards MCF-7, MDA-MB-231, HepG2, LO2 and B16 cells are 2.7 μM, 21.21 μM, 18.70 μM, 41.11μM and 22.68 μM, respectively. PROTAC B-Raf degrader 1 (5 or 10 μM) can accelerate the degradation of B-Raf by recruiting ubiquitin-proteasome system, and further affects the expression of Mcl-1, a downstream protein of B-Raf. MCF-7 cells achieve an apoptosis rate of 76.70% (64.00% early apoptosis, 12.70% late apoptosis) after 24 h incubation of PROTAC B-Raf degrader 1 with the concentration of 20 μM. PROTAC B-Raf degrader 1 arrests cell cycle at the G2/M phase. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Cytotoxicity AssayCell Line: Human MCF-7 breast cancer cell line, MDA-MB-231 breast cancer cells, human HepG2 hepatoma cells, human normal LO2 liver cells, B16 cells. Concentration: 0-200 μM. Incubation Time: 72 hours. Result: The IC 50 values are 2.7 μM, 21.21 μM, 18.70 μM, 41.11μM and 22.68 μM in MCF-7, MDA-MB-231, HepG2, LO2 and B16 cells, respectively. Western Blot AnalysisCell Line: Human MCF-7 breast cancer cell line. Concentration: 5 or 10 μM. Incubation Time: 24 hours. Result: Effectively induced the degradation of B-Raf and impacted the expression of Mcl-1. Apoptosis AnalysisCell Line: Human MCF-7 breast cancer cell line. Concentration: 2.7-20 μM. Incubation Time: 24 hours. Result: Achieved an apoptosis rate of 76.70% (64.00% early apoptosis, 12.70% late apoptosis) after 24 h incubation with the concentration of 20 μM. Cell Cycle AnalysisCell Line: Human MCF-7 breast cancer cell line. Concentration: 20 μM. Incubation Time: 24 hours. Result: 1.94% cells were arrested at G1 phase, 8.20% at S phase, and 89.86% at G2/M phase.
