Basic information Abstract Biological activity In vitro In vivo References Safety Related Supplier
ChemicalBook >  Product Catalog >  Biochemical Engineering >  Inhibitors >  Mitogen-activated protein kinase (MAPK) >  Raf inhibitors >  N-[3-[(5-Chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)carbonyl]-2,4-difluorophenyl]-1-propanesulfonamide

N-[3-[(5-Chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)carbonyl]-2,4-difluorophenyl]-1-propanesulfonamide

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.

Basic information Abstract Biological activity In vitro In vivo References Safety Related Supplier
N-[3-[(5-Chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)carbonyl]-2,4-difluorophenyl]-1-propanesulfonamide Basic information
N-[3-[(5-Chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)carbonyl]-2,4-difluorophenyl]-1-propanesulfonamide Chemical Properties
  • Density 1.55
  • storage temp. +2C to +8C
  • form Orange-yellow solid
  • pka6.20±0.10(Predicted)
N-[3-[(5-Chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)carbonyl]-2,4-difluorophenyl]-1-propanesulfonamide Usage And Synthesis
  • AbstractPLX-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 activityPLX4720 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 vitroPLX-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 vivoOral 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.
  • Referenceshttp://www.cellagentech.com/PLX-4720/
  • UsesPLX4720 is a selective inhibitor of mutant B-RAF and its analog, PLX4032, is currently undergoing clinical trials in melanoma.
  • UsesLabelled PLX4720. It is a selective inhibitor of mutant B-RAF and its analog, PLX4032, is currently undergoing clinical trials in melanoma.
  • UsesA potent and selective inhibitor of B-RafV600E and c-Raf-1Y340D/Y341D with IC50s of 13 nM and 6.7 nM, respectively.
  • DefinitionChEBI: 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).
N-[3-[(5-Chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)carbonyl]-2,4-difluorophenyl]-1-propanesulfonamide(918505-84-7)Related Product Information
N-[3-[(5-Chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)carbonyl]-2,4-difluorophenyl]-1-propanesulfonamideSupplierMore
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    CAS:918505-84-7
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    CAS:918505-84-7
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