Sorafenib

In this article, we will discuss Sorafenib (Mechanism of Action). So, let’s get started.

Mechanism of Action

Sorafenib is a kinase inhibitor that decreases tumor cell proliferation in vitro. Sorafenib was shown to inhibit multiple intracellular (c-CRAF, BRAF and mutant BRAF) and cell surface kinases (KIT, FLT-3, RET, RET/PTC, VEGFR-1, VEGFR-2, VEGFR-3, and PDGFR-B). Several of these kinases are thought to be involved in tumor cell signaling, angiogenesis and apoptosis. Sorafenib inhibited tumor growth of HCC, RCC, and DTC human tumor xenografts in immunocompromised mice. Reductions in tumor angiogenesis were seen in models of HCC and RCC upon sorafenib treatment, and increases in tumor apoptosis were observed in models of HCC, RCC, and DTC.

Pharmacodynamics

Cardiac Electrophysiology

The effect of Sorafenib 400 mg twice daily on the QTc interval was evaluated in a multi-center, open-label, non-randomized trial in 53 patients with advanced cancer. No large changes in the mean QTc intervals (that is >20 ms) from baseline were detected in the trial. After one 28-day treatment cycle, the largest mean QTc interval change of 8.5 ms (upper bound of two-sided 90% confidence interval. 13.3 ms) was observed at 6 hours post-dose on day 1 of cycle 2.

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