475207-59-1 Usage
Description
Sorafenib tosylate, also known as Sorafenib, is a multikinase inhibitor that was initially developed as a Raf kinase inhibitor. It is available in 200-mg tablets for oral administration and is used in the treatment of renal cell carcinoma (RCC) and colon cancer. Sorafenib tosylate is classified as a multikinase inhibitor due to its action on various kinase enzymes, including PDGF-R, VEGF-R, Kit, and Raf. It has a bioavailability of 39% to 48%, and its metabolism is mediated by CYP3A4, resulting in eight identified metabolites, including the N-oxide, which is equally active with the parent compound. Sorafenib tosylate is highly protein-bound (99.5%) and is eliminated primarily in the feces (77%), with 19% appearing in the urine as glucuronides (UGT1A1). It has an elimination half-life of 24 to 48 hours. The most common toxicity is skin rash, which usually occurs within the first six weeks of therapy. Other adverse effects include hypertension, fatigue, increased wound healing time, and an increased risk of bleeding.
Uses
1. Used in Oncology:
Sorafenib tosylate is used as an anticancer agent for the treatment of renal cell carcinoma (RCC) and colon cancer. It acts as a multikinase inhibitor, targeting various kinase enzymes such as Raf-1, B-Raf, VEGFR-2, Flk-1 (VEGFR), PDGFR, and Raf kinases. By inhibiting these enzymes, Sorafenib tosylate modulates the activation of the MAPK pathway and ERK phosphorylation, inducing caspase-independent apoptosis in cancer cells and exerting inhibitory effects on tumor growth and progression.
2. Used in Drug Development:
Sorafenib tosylate serves as a valuable compound in the development of novel drug delivery systems and therapeutic strategies for cancer treatment. Its potent inhibitory effects on multiple kinases make it a promising candidate for combination therapies and the development of targeted cancer treatments.
Brand Name:
Nexavar (Bayer)
Indications and Usage
Sorafenib tosylate is a new type of multi-target antitumor drug, was developed by the German Bayer Pharmaceuticals, and displayed expansive antitumor activity in preclinical animal tests. Sorafenib tosylate is mainly used in advanced liver cancer treatment and is well tolerated.
Mechanisms of Action
Sorafenib tosylate can simultaneously affect tumor cells and tumor blood vessels. It has a double antitumor effect: it can block the cell signal transduction pathways mediated by RAF/MEK/ERK to directly inhibit tumor cell growth, while also inhibiting VEGF and platelet derived growth factors (PDGF) receptors to prevent the formation of new tumor blood vessels, thus indirectly inhibiting tumor cell growth.
Clinical Research
In a stage three randomized clinical study of American and European treatments for advanced kidney cancer, 903 cases advanced kidney patients who had experienced one unsuccessful systematic treatment (biological immunity or chemotherapy) were randomly split into two groups. One group received sorafenib tosylate, while the other received a placebo. Mid-term analysis found already 222 deaths and the objective efficacy of the two groups to be 10% and 2%, while 74% and 53% of patients had stabilized conditions. The sorafenib tosylate group’s survival period was longer than that of the placebo group, with the risk ratio as 0.72. However, this different does not have statistical significance, as this is only a mid-term analysis, and final analysis after treatment will yield the correct survival period comparison.
602 advanced liver cancer patients selected from the USA, Europe, Australia, and other countries and areas, who did not receive systematic treatment, were included in a study. Results showed that compared to the placebo, taking sorafenib tosylate could extend their total survival period of patients with late stage or primary liver cancer by about 44% and their extend disease progression period by about 73%.
Adverse reactions
Manageable diarrhea, rashes, fatigue, hand-foot syndrome, hypertension, alopecia, nausea, vomiting, and loss of appetite.
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
Check Digit Verification of cas no
The CAS Registry Mumber 475207-59-1 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 4,7,5,2,0 and 7 respectively; the second part has 2 digits, 5 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 475207-59:
(8*4)+(7*7)+(6*5)+(5*2)+(4*0)+(3*7)+(2*5)+(1*9)=161
161 % 10 = 1
So 475207-59-1 is a valid CAS Registry Number.
