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S-8502 Sorafenib, p-Toluenesulfonate Salt, >99%       Prices Reduced (September 2007)

[Sorafenib Tosylate] [Bay 43-9006] [Nexavar]

M.W. 637.04

C21H16ClF3N4O3•C7H8O3S

[475207-59-1]

M.I. 14:  8720

Storage:  Store at or below -20 ºC.  Solubility:  Very soluble in DMSO, up to about 200 mg/mL; very poorly soluble in water or ethanol.  Disposal:  A

View the MSDS for this product

• Sorafenib (Bay 43-9006) is a novel bi-aryl urea compound that inhibits cell proliferation by targeting the ERK pathway and angiogenesis by targeting the receptor tyrosine kinases VEGFR-2 and PDGFR-β and their associated signaling cascades.  Although sorafenib was initially developed as a Raf kinase inhibitor (IC50 = 6 nM), it has since been shown to have activity against many receptor tyrosine kinases involved in tumorigenesis and angiogenesis including FGFR-1, wt BRAF and V599E mutant BRAF, as well as members of the so-called "split kinase" family:  VEGFR-2, VEGFR-3, PDGFR-β, c-KIT, and Flt3.  However, sorafenib is not active against erbB1, erbB2, ERK-1, MEK-1, EGFR, HER-2, IGFR-1, c-MET, c-yes, PKB, PKA, cdk1/cyclinB, PKC, and pim-1.  In cellular mechanistic assays, sorafenib decreased basal phosphorylation of the ERK pathway in melanoma, breast, colon, and pancreatic tumor cell lines.  Wilhelm, S.M., et al.  "BAY 43-9006 Exhibits Broad Spectrum Oral Antitumor Activity and Targets the RAF/MEK/ERK Pathway and Receptor Tyrosine Kinases Involved in Tumor Progression and Angiogenesis."  Cancer Res. 64:  7099-7109 (2004).

  BAY 43-9006 inhibits the RAF/MEK/ERK pathway and receptor tyrosine kinases
  involved in tumor angiogenesis (adapted from Wilhelm, S.M., et al. 2004)

  Biochemical Assay *	IC50 (nM) ± SD
  Raf-1 **	6 ± 3
  BRAF wild-type	22 ± 6
  V599E BRAF mutant	38 ± 9
  VEGFR-2	90 ± 15
  mVEGFR-2 (flk-ss1)	15 ± 6
  mVEGR-3	20 ± 6
  mPDGFR-β	57 ± 20
  Flt-3	58 ± 20
  c-KIT	68 ± 21
  FGFR-1	580 ± 100
  ERK-1, MEK-1, EGFR, HER-2, IGFR-1, c-met, PKB, PKA, cdk1/cyclinB, PKC, PKC, pim-1	>10,000
  Cellular Mechanism
  MDA MB 231 MEK phosphorylation (human breast)	40 ± 20
  MDA MB 231 ERK 1/2 phosphorylation (human breast)	90 ± 26
  BxPC-3 ERK 1/2 phosphorylation (human pancreatic)	1,200 ± 165
  LOX ERK 1/2 phosphorylation (human melanoma)	880 ± 90
  VEGFR-2 phosphorylation (human, NIH 3T3 cells)	30 ± 21
  VEGF-ERK 1/2 phosphorylation (human, HUVEC)	60 ± 26
  PDGFR-β phosphorylation (human HAoSMC)	80 ± 40
  mVEGFR-3 phosphorylation (mouse, HEK-293 cells)	100 ± 80
  Flt-3 phosphorylation (human ITD, HEK-293 cells)	20 ± 10
  Cellular Proliferation
  MDA MB 231 (10% FCS)	2,600 ± 810
  PDGF-BB HAoSMC	280 ± 140

  * Kinase assays were carried out at ATP concentrations at or below Km (1-10 µM)

  ** Lck-activated NH2-terminal-truncated Raf-1

• Sorafenib is more potent in a cellular system (IC50 = 20 nM) than in an enzyme assay (IC50 = 107 nM).  Guo, J., et al.  "Inhibition of phosphorylation of the colony-stimulating factor-1 receptor (c-Fms) tyrosine kinase in transfected cells by ABT-869 and other tyrosine kinase inhibitors."  Mol. Cancer Ther. 5:  1007-1013 (2006).

• Sorafenib potently inhibited activation of the MAPK pathway and ERK phosphorylation in human cancer cell lines, irrespective of whether they harbored K-ras mutations, V599EB-Raf, or both.  Wilhelm, S., et al.  "The novel Raf inhibitor Bay 43-9006 blocks signaling and proliferation in BRAF mutant and wildtype melanoma and colorectal tumor cell lines."  Proc. Am. Assoc. Cancer Res. 44:  106609 (2003).

• Sorafenib inhibited various nonkinase targets, including adenosine A3, dopamine D1, and muscarine M3 receptors, albeit at much higher (micromolar) concentrations than kinase targets.  Carter, C., et al.  "Investigators Brochure Bay 43-9006/ Raf Kinase Inhibitor."  Version No. 5. West Haven, CT, Bayer Pharmaceuticals Corporation, 2004.

• Sorafenib tosylate is the active ingredient in the drug sold under the trade name Nexavar®.  This drug is currently approved for use in patients with advanced renal cell cancer.

• Sold for laboratory or manufacturing purposes only; not for human, veterinary, food, or household use.

• This product is offered for R&D use in accordance with (i) 35 USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. Patents Act of 1977 in the U.K.; (v) Section 68B of the Patents Act of 1953 in New Zealand; (vi) such related legislation and/or case law as may be or become applicable in the aforementioned countries; and (vii) such similar laws and rules as may apply in various other countries.

• Not available in some countries; not available to some institutions; not available for some uses.