Uveal Melanoma (UM) is the most common primary intraocular malignancy of the adult eye, with an incidence of five to six cases per million. Despite aggressive local management of primary UM, the development of metastases is common and occurs in ~50% of patients. There are currently no effective treatment options for metastatic disease and median survival is around nine months. Genetic analysis of UM samples reveals the presence of activating mutations in the Gq alpha subunits, GNAQ and GNA11. One of the key downstream targets of the constitutively active Gq alpha subunits is the protein kinase C (PKC) signaling pathway.<br/>We describe the discovery of NVP-LXS196, a potent, selective PKC inhibitor. The lead series was optimzed for kinase and off target selectivity to afford a compound that is rapidly absorbed and well tolerated in pre-clinical species. NVP-LXS196 is currently in Phase I clinical trials to assess the safety, tolerability and pharmacokinetic profile in metastatic uveal melanoma patients.

NVP-LXS196, a novel PKC inhibitor for the treatment of uveal melanoma

253rd National Meeting (2017)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.