JNJ-10229570

JNJ-10229570 is an antagonist of melanocortin receptor 1 (MC1R) and melanocortin receptor 5 (MC5R), which inhibits sebaceous gland differentiation and the production of sebum-specific lipids. JNJ-10229570 inhibits the binding of ¹²⁵I-NDP-α-MSH to cells expressing human MC1R and MC5R, with IC₅₀ values of 270 nM and 200 nM, respectively. IC50 & Target: IC50: 270 nM (human MC1R), 200 nM (human MC5R)^[1]. In Vitro: JNJ-10229570 dose dependently inhibits the production of sebaceous lipids in cultured primary human sebocytes. JNJ-7818369 inhibits the binding of ¹²⁵I-NDP-α-MSH to cells expressing human MC1R and MC5R, with IC₅₀s of 270±120 and 200±50 nM, respectively. Nearly-identical results are obtained with the free base form of the compound. Binding to MC4R of both forms of the compound is equipotent, with IC₅₀s of 240±170 nM. JNJ-10229570-treated cells show strong inhibition of lipid granules at 0.01 μM, and complete inhibition at 0.05 μM^[1]. In Vivo: Topical treatment with JNJ-10229570 of human skins transplanted onto SCID mice result in a marked decrease in sebum-specific lipid production, sebaceous gland's size and the expression of the sebaceous differentiation marker epithelial-membrane antigen (EMA). Topical treatment with 0.05% JNJ-10229570 leads to a distinct reduction in both the steady-state and the newly-synthesized sebum-specific lipids, with lesser effects on triglycerides and cholesterol^[1].