Sorafenib-d₃

Sorafenib-d₃ is intended for use as an internal standard for the quantification of sorafenib (Item No. 10009644) by GC- or LC-MS. Sorafenib is a multi-kinase inhibitor that inhibits Raf-1 and B-RAF (IC₅₀s = 6 and 22 µM, respectively), as well as the receptor tyrosine kinases VEGFR2, VEGFR3, PDGFRβ, FLT3, and c-Kit (IC₅₀s = 90, 15, 20, 57, and 58 nM, respectively).^1,2 It is selective for these kinases over 12 other kinases, including ERK1, MEK1, EGFR, and HER2 (IC₅₀s = >10 µM for all).² Sorafenib inhibits proliferation of PLC/PRF/5 and HepG2 cells (IC₅₀s = 6.3 and 4.5 µM, respectively) and induces apoptosis in these cells.³ It completely inhibits tumor growth in a PLC/PRF/5 mouse xenograft model when administered at a dose of 30 mg/kg and reduces basic FGF-induced angiogenesis in a Matrigel^™ assay in vivo.^3,4 Sorafenib (10 µM) induces ferroptotic cell death in HT-1080 fibrosarcoma cells, an effect that can be blocked by the ferroptosis inhibitors ferrostatin-1 (Item No. 17729), deferoxamine (Item No. 14595), and β-mercaptoethanol.⁵ It inhibits glutamate release by the system x_c^- cystine/glutamate transporter in HT-1080 cells when used at concentrations ranging from 2.5 to 10 µM, decreases glutathione levels, and increases lipid peroxidation. Sorafenib also inhibits replication of hepatitis C virus (HCV) in Huh7.5 cells (IC₅₀ = 7.2 µM).⁶ Formulations containing sorafenib have been used in the treatment of hepatocellular, renal cell, and thyroid carcinomas.

WARNING This product is not for human or veterinary use.

1. Lyons, J.F., Wilhelm, S., Hibner, B., et al. Discovery of a novel Raf kinase inhibitor. Endocr. Relat. Cancer 8(3), 219-225 (2001).

2. Wilhelm, S.M., Carter, C., and Tang, L. 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(19), 7099-7109 (2004).

3. Liu, L., Cao, Y., Chen, C., et al. Sorafenib blocks the RAF/MEK/ERK pathway, inhibits tumor angiogenesis, and induces tumor cell apoptosis in hepatocellular carcinoma model PLC/PRF/5. Cancer Res. 66(24), 11851-11858 (2006).

4. Murphy, D.A., Makonnen, S., Lassoued, W., et al. Inhibition of tumor endothelial ERK activation, angiogenesis, and tumor growth by sorafenib (BAY43-9006). Am. J. Pathol. 169(5), 1875-1885 (2006).

5. Dixon, S.J., Patel, D.N., Welsch, M., et al. Pharmacological inhibition of cystine-glutamate exchange induces endoplasmic reticulum stress and ferroptosis. Elife 3, e02523 (2014).

6. Himmelsbach, K., Sauter, D., Baumert, T.F., et al. New aspects of an anti-tumour drug: Sorafenib efficiently inhibits HCV replication. Gut 58(12), 1644-1653 (2009).