PLX-4720 displays >10 times selectivity against wild type B-Raf, and >100 times selectivity over other kinases such as Frk, Src, Fak, FGFR, and Aurora A with IC50 of 1.3-3.4 μM. PLX-4720 significantly inhibits the ERK phosphorylation in cell lines bearing B-RafV600E with IC50 of 14-46 nM, but not the cells with wild-type B-Raf. PLX-4720 significantly inhibits the growth of tumor cell lines bearing the B-RafV600E oncogene, such as COLO205, A375, WM2664, and COLO829 with GI50 of 0.31 μM, 0.50 μM, 1.5 μM, and 1.7 μM, respectively. In addition, PLX-4720 treatment at 1 μM induces cell cycle arrest and apoptosis exclusively in the B-RafV600E-positive 1205Lu cells, but not in the B-Raf wild-type C8161 cells. PLX-4720 treatment (10 μM) significantly induces >14-fold expression of BIM in the PTEN+ cells, compared with the PTEN- cell lines (4-fold), giving an explanation of the resistance of PTEN- cells to PLX-4720-induced apoptosis.
Raf Inhibitors Related Products:
Vemurafenib; Debrafenib; Regorafenib; GDC-0879; RAF265 (CHIR-265); AZ-628; SB590885; ZM 336372; TAK-632; B-Raf IN 1; AZ304; Dabrafenib Mesylate; RAF709; LY3009120; RO5126766; Doramapimod; MLN2480; GW5074