Regorafenib

• CAT Number: A000931
• CAS Number: 755037-03-7
• Molecular Formula: C₂₁H₁₅ClF₄N₄O₃
• Molecular Weight: 482.81
• Purity: ≥95%
• Target: c-RET
• Solubility: >25mg/mL in DMSO
• Storage: 3 years -20C powder
• InChI: InChI=1S/C21H15ClF4N4O3/c1-27-19(31)18-10-13(6-7-28-18)33-12-3-5-17(16(23)9-12)30-20(32)29-11-2-4-15(22)14(8-11)21(24,25)26/h2-10H,1H3,(H,27,31)(H2,29,30,32)
• InChIKey: FNHKPVJBJVTLMP-UHFFFAOYSA-N
• SMILES: CNC(=O)C1=NC=CC(=C1)OC2=CC(=C(C=C2)NC(=O)NC3=CC(=C(C=C3)Cl)C(F)(F)F)F

Regorafenib, also known as BAY 73-4506 ; is a n orally bioavailable small molecule with potential antiangiogenic and antineoplastic activities. Regorafenib binds to and inhibits vascular endothelial growth factor receptors (VEGFRs) 2 and 3, and Ret, Kit, PDGFR and Raf kinases, which may result in the inhibition of tumor angiogenesis and tumor cell proliferation. Regorafenib demonstrated to increase the overall survival of patients with metastatic colorectal cancer and has been approved by the US FDA on September 27, 2012.

Reference

1: Ravi S, Singal AK. Regorafenib: an evidence-based review of its potential in patients with advanced liver cancer. Core Evid. 2014 Jul 17;9:81-7. doi: 10.2147/CE.S48626. eCollection 2014. Review. PubMed PMID: 25114628; PubMed Central PMCID: PMC4109634.2: Abdel-Rahman O, Fouad M. Risk of cardiovascular toxicities in patients with solid tumors treated with sunitinib, axitinib, cediranib or regorafenib: An updated systematic review and comparative meta-analysis. Crit Rev Oncol Hematol. 2014 Jul 1. pii: S1040-8428(14)00114-0. doi: 10.1016/j.critrevonc.2014.06.003. [Epub ahead of print] Review. PubMed PMID: 25028151.3: Khan G, Moss RA, Braiteh F, Saltzman M. Proactive strategies for regorafenib in metastatic colorectal cancer: implications for optimal patient management. Cancer Manag Res. 2014 Mar 4;6:93-103. doi: 10.2147/CMAR.S52217. eCollection 2014. Review. PubMed PMID: 24623990; PubMed Central PMCID: PMC3949557.4: De Wit M, Boers-Doets CB, Saettini A, Vermeersch K, de Juan CR, Ouwerkerk J, Raynard SS, Bazin A, Cremolini C. Prevention and management of adverse events related to regorafenib. Support Care Cancer. 2014 Mar;22(3):837-46. doi: 10.1007/s00520-013-2085-z. Epub 2013 Dec 14. Review. PubMed PMID: 24337717; PubMed Central PMCID: PMC3913844.5: Lyseng-Williamson KA. Regorafenib: a guide to its use in advanced gastrointestinal stromal tumor (GIST) after failure of imatinib and sunitinib. BioDrugs. 2013 Oct;27(5):525-31. doi: 10.1007/s40259-013-0061-2. Review. PubMed PMID: 23975637.6: Regorafenib (Stivarga) for metastatic colorectal cancer and GIST. Med Lett Drugs Ther. 2013 Apr 29;55(1415):e36. Review. PubMed PMID: 23836345.7: Sirohi B, Philip DS, Shrikhande SV. Regorafenib: carving a niche in the crowded therapeutic landscape. Expert Rev Anticancer Ther. 2013 Apr;13(4):385-93. doi: 10.1586/era.13.12. Review. PubMed PMID: 23560833.8: Davis SL, Eckhardt SG, Messersmith WA, Jimeno A. The development of regorafenib and its current and potential future role in cancer therapy. Drugs Today (Barc). 2013 Feb;49(2):105-15. doi: 10.1358/dot.2013.49.2.1930525. Review. PubMed PMID: 23462625.9: Roman D, Whiteside R. Regorafenib: Adding to the Armamentarium for Refractory Colorectal Cancer and GIST. J Adv Pract Oncol. 2013 Mar;4(2):118-22. Review. PubMed PMID: 25031991; PubMed Central PMCID: PMC4093419.10: Aprile G, Macerelli M, Giuliani F. Regorafenib for gastrointestinal malignancies : from preclinical data to clinical results of a novel multi-target inhibitor. BioDrugs. 2013 Jun;27(3):213-24. doi: 10.1007/s40259-013-0014-9. Review. PubMed PMID: 23435872.11: Strumberg D, Schultheis B. Regorafenib for cancer. Expert Opin Investig Drugs. 2012 Jun;21(6):879-89. doi: 10.1517/13543784.2012.684752. Review. PubMed PMID: 22577890.