Discovery of EBI-907: A highly potent and orally active B-RafV600E inhibitor for the treatment of melanoma and associated cancers

A novel series of pyrazolo[3,4-c]isoquinoline derivatives was discovered as B-RafV600E inhibitors through scaffold hopping based on a literature lead PLX4720. Further SAR exploration and optimization led to the discovery of potent B-RafV600E inhibitors with good oral bioavailability in rats and dogs. One of the compounds EBI-907 (13g) demonstrated excellent in vivo efficacy in B-RafV600E dependent Colo-205 tumor xenograft models in mouse and is under preclinical studies for the treatment of melanoma and B-RafV600E associated cancers.

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