ML00253764 hydrochloride

ML-00253764 is a nonpeptidic melanocortin receptor 4 (MC4R) antagonist with a Ki and IC50 of 0.16 µM and 0.103 µM, respectively. Brain penetrant[1].

Research Areas >> Cancer

Research Areas >> Endocrinology

ML-00253764 displaces NDP-α-MSH binding with a mean IC50 of 0.32 μM, 0.81 μM and 2.12 μM for hMC4-R, hMC3-R and hMC5-R, respectively[1]. ML-00253764 (100 µM) decreases cAMP production induced by [NLE4,D-Phe7]-α-melanocyte stimulating hormone ([NDP]-α-MSH) by 20% in MC4R-expressing HEK293 cell membranes, but has no effect on cAMP levels in MC3R- or MC5R-expressing membranes[1].

ML-00253764 (subcutaneous injection; 3, 10, or 30 mg/kg; once daily) shows protection against tumor-induced body weight loss upon chronic, peripheral dosing in CT-26 tumor bearing BALB/c mice[1]. ML-00253764 dissolves in polyethylene glycol 200/saline (1:10) in a volume of 10 ml/kg[1]. Animal Model: CT-26 tumor bearing BALB/c mice[1] Dosage: 3, 10, or 30 mg/kg Administration: Subcutaneous injection; 3, 10, or 30 mg/kg; once daily Result: Reduced tumor-induced weight loss in a mouse model.

[1]. Vos TJ, et al. Identification of 2-[2-[2-(5-bromo-2- methoxyphenyl)-ethyl]-3-fluorophenyl]-4,5-dihydro-1H-imidazole (ML00253764), a small molecule melanocortin 4 receptor antagonist that effectively reduces tumor-induced weight loss in a mouse model. J Med Chem. 2004 Mar 25;47(7):1602-4.