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Release time：2017/06/20 Click rate：
|PLX-4720 Basic information|
|Synonyms:||N-[3-[(5-Chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)carbonyl]-2,4-difluorophenyl]-1-propanesulfonamide;PLX-4720;N-(3-(5-Chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluorophenyl)propane-1-sulfonamide;1-PropanesulfonaMide, N-[3-[(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)carbonyl]-2,4-difluorophenyl]-;N-[3-[(5-Chloro-1H-pyrrol...;N-[3-[(5-Chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)carbonyl]-2,4-difluorophenyl]-1-propanesulfonamide PLX 4720;PLX 4720 N-[3-[(5-Chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)carbonyl]-2,4-difluorophenyl]-1-propanesulfonamide;PLX4720, >=98%|
|Product Categories:||Aromatics;Heterocycles;Intermediates & Fine Chemicals;Isotope Labelled Compounds;Pharmaceuticals;Sulfur & Selenium Compounds;Inhibitors|
|PLX-4720 Chemical Properties|
|PLX-4720 Usage And Synthesis|
PLX-4720 is an orally-available, ATP-competitive, highly selective, azaindole-based inhibitor of B-Raf (V600E) with IC50 value of 13 nM. PLX-4720 has additional activity towards mutant forms of c-Raf-1 (Y340D, Y341D) at an IC50 of 6.7 nM, with modest single micromolar activity versus kinases such as FRK, CSK, SRC, FGFR, KDR< HGK, and Aurora A. PLX-4720 has shown preclinical activity in melanoma and thyroid cancer models.
PLX-4720 preferentiallly inhibits ERK phosphorylation in tumor cell lines bearing the V600E allele. In melanoma models it induces cell cycle arrest and apoptosis exclusively in B-Raf (V600E)-positive cells.
In an orthotopic 8505c human thyroid cancer mice model, PLX-4720 caused significant reduction in tumor growth (>90%) and dramatically decreased lung metastases.
|Biological activity||PLX4720 is a potent and selective inhibitor of B-RafV600E with IC50 of 13 nM in a cell-free assay, equally potent to c-Raf-1(Y340D and Y341D mutations), 10-fold selectivity for B-RafV600E than wild-type B-Raf.|
|In vitro||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.|
|In vivo||Oral administration of PLX-4720 at 20 mg/kg/day induces significant tumor growth delays and regressions in B-RafV600E-dependent COLO205 tumor xenografts, without obvious adverse effects in mice even at dose of 1 g/kg. PLX-4720 at 100 mg/kg twice daily almost completely eliminates the 1205Lu xenografts bearing B-RafV600E, while has no activity against C8161 xenografts bearing wild-type B-Raf. The anti-tumor effects of PLX-4720 correlate with the blockade of MAPK pathway in those cells harboring the V600E mutation. PLX-4720 treatment at 30 mg/kg/day significant inhibits the tumor growth of 8505c xenografts by >90%, and dramatically decreases distant lung metastases.|
|Usage||PLX4720 is a selective inhibitor of mutant B-RAF and its analog, PLX4032, is currently undergoing clinical trials in melanoma.|
|Usage||Labelled PLX4720. It is a selective inhibitor of mutant B-RAF and its analog, PLX4032, is currently undergoing clinical trials in melanoma.|
|Usage||A potent and selective inhibitor of B-RafV600E and c-Raf-1Y340D/Y341D with IC50s of 13 nM and 6.7 nM, respectively.|
|Definition||ChEBI: A pyrrolopyridine that is vemurafenib in which the p-chlorophenyl group has been replaced by chlorine. It is a potent and selective inhibitor of the Raf kinase B-Raf(V600E).|