Sorafenib tosylate

Description

Sorafenib (475207-59-1) was initially developed as a Raf kinase inhibitor, IC50 = 6 nM, but has been shown to inhibit many receptor tyrosine kinases including BRAF (IC50 = 22 nM); VEGFR-2 (IC50 = 90 nM); VEGFR-3 (IC50 = 20 nM); PDGFR-β (IC50 = 57 nM); Flt3 (IC50 = 58 nM); c-KIT (IC50 = 68 nM); FGFR-1 (IC50 = 580 nM).1?Paradoxically more potent in a cellular assay (IC50 = 20 nM) compared to an isolated enzyme assay (IC50 = 107 nM) for c-Fms.2?Inhibits activation of MAPK pathway and ERK phosphorylation.3?Induces caspase-independent apoptosis in melanoma cells.4?Sorafenib is a clinically useful anticancer agent.

The Uses of Sorafenib tosylate

Sorafenib Tosylate (Bay 43-9006, Nexavar) is a small molecular inhibitor of VEGFR, PDGFR, c-Raf and B-Raf with IC50s of 18 nM, 10 nM, 3 nM and 15 nM, respectively.

Definition

ChEBI: Sorafenib tosylate is an organosulfonate salt. It contains a sorafenib.

What are the applications of Application

Sorafenib Tosylate is an inhibitor of Flk-1 (VEGFR), PDGFR and Raf kinases used for the treatment of human hepatocellular carcinoma.

brand name

Nexavar (Bayer).

General Description

Sorafenib is available in 200-mg tablets for oral administrationand is used in the treatment of RCC and colon cancer.The agent is classified as a multikinase inhibitor because ofits action on numerous kinase enzymes including thePDGF-R, VEGF-R, Kit, and Raf. Sorafenib is 39% to 48% bioavailable and CYP3A4-mediated metabolism giveseight identified metabolites including the N-oxide, which isequally active with the parent. However, the majority of thedrug in plasma is present as the parent compound.Sorafenib is highly protein bound (99.5%). The drug iseliminated primarily in the feces (77%) with 19% appearingin the urine as glucuronides (UGT1A1) and has a eliminationhalf-life of 24 to 48 hours. The most commonly seentoxicity is skin rash that normally occurs within the first6 weeks of therapy. Other adverse effects include hypertension,fatigue, increased wound healing time, and increasedrisk of bleeding.

Clinical Use

Sorafenib is used to treat late-stage kidney cancer (advanced renal cell carcinoma), liver cancer (hepatocellular carcinoma) that cannot be treated by surgery, and differentiated thyroid cancer that has come back or spread to other parts of your body. Sorafenib is an antineoplastic (cancer) agent. It interferes with the growth of cancer cells, which are eventually destroyed by the body.

Side Effects

The side effects of Sorafenib tosylate include Bleeding gums, blistering, peeling, redness, or swelling of the palms of the hands or bottoms of the feet, bloating of the abdomen or stomach, blood in the urine or stools, clay-colored stools, coughing up blood, difficulty with breathing or swallowing, increased menstrual flow or vaginal bleeding.

References

1) Wilhelm et al. (2004), 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 2) Guo et al. (2006), 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 3) Wilhelm et al. (2003), The novel Raf inhibitor BAY 43-9006 blocks signaling and proliferation in BRAF mutant and wildtype melanoma and colorectal tumor cell lies; Proc. Am. Assoc. Cancer Res., 44 106609 4) Panka et al. (2006), The Raf inhibitor BAY 43-9006 (Sorafenib) induces caspase-independent apoptosis in melanoma cells; Cancer Res., 66 1611