产品描述:
PROTAC RAF degrader 1 is a proteolysis-targeting chimera (PROTAC) that contains the inhibitor of mutant V600E and wild-type B-RAF vemurafenib (PLX4032; Item No. 10618) conjugated to VHL ligand 1 (Item No. 21591).{69768} It selectively induces the degradation of B-RAF containing a valine-to-glutamate substitution at position 600 (B-RAFV600E) over wild-type B-RAF in SK-MEL-239 melanoma cells at 10 to 1,000 nM but non-selectively inhibits the activity of wild-type B-RAF and a panel of mutant B-RAF isoforms (IC50s = 5.8 and 1.87 nM). PROTAC RAF degrader 1 reduces cell viability of SK-MEL-28, SK-MEL-239, and SK-MEL-246 melanoma cells (EC50s = 215, 37, and 243 nM, respectively). In vivo, PROTAC RAF degrader 1 (50 mg/kg twice per day) reduces tumor growth and volume in an SK-MEL-246 mouse xenograft model.