Recent progress in the identification of BRAF inhibitors as anti-cancer agents

•BRAF is mutated at high frequency in many cancers especially melanoma.•BRAF is an attractive target for medicinal chemists.•BRAF inhibitors displayed potent anticancer activity against mutant tumors.•The present review provides overview about the progress in the discovery of BRAF inhibitors.

The “RAS/BRAF/MEK/ERK” pathway has been associated with human cancers due to the frequent oncogenic mutations identified in its members. In particular, BRAF is mutated at high frequency in many cancers especially melanoma. This mutation leads to activation of the MAPK signaling pathway, inducing uncontrolled cell proliferation, and facilitating malignant transformation. All these facts make BRAF an ideal target for antitumor therapeutic development. Many BRAF inhibitors have been discovered during the last decade and most of them exhibit potent antitumor activity especially on tumors that harbor BRAFV600E mutations. Some of these compounds have entered clinical trials and displayed encouraged results. The present review highlights the progress in identification and development of BRAF inhibitors especially during the last five years.

Graphical abstractThe present review highlights the progress in identification and development of potent, selective and specific inhibitors of BRAF especially during the last five years.Figure optionsDownload full-size imageDownload as PowerPoint slide