Darovasertib

Darovasertib (LXS196) is a potent, selective and orally active protein kinase C (PKC) inhibitor, with IC₅₀ values of 1.9 nM, 0.4 nM and 3.1 μM for PKCα, PKCθ and GSK3β, respectively. Darovasertib has the potential for uveal melanoma research^[1][2]. In Vitro: Upon oral administration, protein kinase C inhibitor LXS196 binds to and inhibits PKC, which prevents the activation of PKC-mediated signaling pathways. This may lead to the induction of cell cycle arrest and apoptosis in susceptible tumor cells. PKC, a serine/threonine protein kinase overexpressed in certain types of cancer cells, is involved in tumor cell differentiation, proliferation, invasion and survival^[1]. In Vivo: Darovasertib (LXS196; compound 9) (15, 30, 75, 150 mg/kg, P.O., mice) shows improved efficacy (regression) in a 92.1 GNAQ uveal melanoma xenograft model in a dose-dependently manner^[2].