Regorafenib-13C-d3

Description

Regorafenib-¹³C-d₃ is intended for use as an internal standard for the quantification of regorafenib by GC- or LC-MS. Regorafenib is an orally bioavailable multi-kinase inhibitor with anticancer activity.¹ It inhibits RET, C-RAF, VEGFR2, c-Kit, VEGFR1, and PDGFRβ with IC₅₀ values of 1.5, 2.5, 4.2, 7, 13, and 22 nM, respectively. Regorafenib also inhibits B-RAF, VEGFR3, FGFR, and Tie2 (IC₅₀s = 28, 46, 202, and 311 nM, respectively) as well as other kinases.^1,2,3 In vivo, regorafenib (10 mg/kg) reduces tumor size in the MDA-MB-231 breast and 786-O renal cancer mouse xenograft models.¹ It also reduces tumor microvessel area and inhibits tumor growth in a panel of mouse xenograft models. Formulations containing regorafenib have been used in the treatment of advanced gastrointestinal stromal tumors and metastatic colorectal cancer.

References

1. Wilhelm, S.M., Dumas, J., Adnane, L., et al. Regorafenib (BAY 73-4506): A new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity Int. J. Cancer 129(1),245-255(2011).
2. Uitdehaag, J.C.M., de Roos, J.A.D.M., van Doornmalen, A.M., et al. Comparison of the cancer gene targeting and biochemical selectivities of all targeted kinase inhibitors approved for clinical use PLoS One 9(3),1-13(2014).
3. Ravi, S., and Singal, A.K. Regorafenib: An evidence-based review of its potential in patients with advanced liver cancer Core Evid. 9,81-87(2014).