Raf proteins are serine/threonine kinases that transduce signals from Ras proteins and amplify them using the MAPK signaling cascade. Mutant forms of B-Raf, one of the primary types of Raf proteins, play a significant role in the development of many cancers.
The mutations that occur in B-Raf, such as V599K or V600E destabilize the protein’s regular interactions, inducing activation and resulting in potentially uncontrolled downstream signaling and cell growth. As a result, the Ras-Raf signaling pathway has become a very interesting target for anticancer chemotherapeutic compounds.
Dabrafenib is a reversible kinase inhibitor that is selective for mutant (V600E) B-Raf. It is an ATP-competitive inhibitor that has been used in the treatment of unresectable or metastatic melanomas, and also shows potential in the treatment of brain metastases. In a 2016 study, results from a phase II trial showed that dabrafenib exhibited significant activity in patients with advanced non-small cell lung cancer harboring the V600E B-Raf mutation. The study also suggested that combining dabrafenib with a MEK inhibitor might be an even more effective treatment for patients with this type of cancer.
LKT Labs sells a number of high purity B-Raf inhibitors, including the following compounds:
Dabrafenib Active in Rare NSCLC Subtype. Cancer Discov. 2016 Jul;6(7):OF4. PMID: 27207893.