JNJ-10229570 (UNII-N9IX402L35) 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.

MC5R (human):200 nM, MC1R (human):270 nM

JNJ-10229570剂量依赖性地抑制培养的初代人类皮脂腺细胞的皮脂生产。JNJ-7818369能够抑制125I-NDP-α-MSH与表达人类MC1R和MC5R的细胞的结合，其IC50分别为270±120 nM和200±50 nM。与该化合物的游离碱基形式获得的结果几乎相同。两种形式的化合物与MC4R的结合均为等效，IC50均为240±170 nM。以0.01 μM处理的JNJ-10229570细胞显示出强烈的脂质颗粒抑制作用，并在0.05 μM时完全抑制。

在SCID鼠体内移植的人类皮肤上进行JNJ-10229570局部治疗，显著减少了特定于皮脂的脂质产生、皮脂腺的大小以及皮脂分化标记物上皮膜抗原(EMA)的表达。与已知的皮脂生成抑制剂flutamide的治疗相比, 在人皮肤/SCID鼠实验系统中用于研究皮脂分泌的表现。

Radioligand binding assays were performed, with CHO-K1 cells over-expressing MC1R, and HEK-293 cells over-expressing MC4R or MC5R, using a single concentration of 125I-NDP-a-MSH and increasing concentrations of JNJ-7818369 or JNJ-10229570. IC50 values for inhibition of radioligand binding were calculated by a non-linear, least squares regression method.

JNJ-10229570 (0.05%) and flutamide (5%) were dissolved in a vehicle of ethanol: propylene glycol (7:3).?20 ml/1.5 cm^2 were applied onto each skin xenograft, starting at three months posttransplantation.?Xenografts were treated once daily, 5 days/week, for 30 34 treatments.?Xenografts were then collected for histological examination and lipid analysis.?Each study was repeated with skin xenografts from at least 3 donors.?The vehicle had no effect on sebaceous glands differentiation or activity.