The Journal of Medicinal Chemistry recently publishes an article titled, “Discovery of Darovasertib, a Pan-PKC Inhibitor for the Treatment of Metastatic Uveal Melanoma”. Uveal melanoma (UM) is the most common primary intraocular malignancy. About half of primary uveal melanoma tumors metastasize but with no standard treatment. Most patients with metastatic uveal melanoma have been found to have mutations in GNAQ or GNA11, that are associated with consistent activation of the protein kinase C (PKC) and mitogen-activated protein kinase (MAPK) pathways.
IDEAYA's Darovasertib (IDE196) is a potent, selective small molecule inhibitor of PKC which stops activating PKC/MEK pathway. Darovasertib is under Phase 2 expansion and Phase 3 registrational trial with Crizotinib in GNAQ/11 metastatic cutaneous melanoma.