TC-MCH 7c

TC-MCH 7c, a phenylpyridone derivative, is an orally available, selective and brain-penetrable MCH1R antagonist with an IC50 of 5.6 nM for hMCH1R[1]. TC-MCH 7c has Kis of 3.4 nM and 3.0 nM of human and mouse MCH1R, respectively[2].

Signaling Pathways >> GPCR/G Protein >> MCHR1 (GPR24)

Research Areas >> Metabolic Disease

IC50: 5.6 nM (hMCH1R)[1] Ki: 3.4 nM (hMCH1R) and 3.0 nM (mouse MCH1R)[1]

TC-MCH 7c has an IC50 of 9.7 μM for MCH1R in [Ca2+]i mobilization[1]. TC-MCH 7c has IC50s of 23 nM and 9.0 μM for FLIPR and hERG, respectively[2].

TC-MCH 7c (oral; 3-30 mg/kg; once-daily for 1.5 months) exhibits excellent body weight reduction in a dose-dependent manner in DIO mice model[1]. TC-MCH 7c (oral; 3-30 mg/kg) with 30 mg/kg has plasma concentrations of 5.1, 1.8, and 0.7 μM at 2, 15, and 24 hours, respectively[2]. Animal Model: C57BL/6J DIO mice[1] Dosage: 3, 10 and 30 mg/kg Administration: Oral; once-daily for 1.5 months Result: Exhibited excellent body weight reduction in a dose-dependent manner. Animal Model: Diet-induced obesity mice[2] Dosage: 3, 10 and 30 mg/kg (Pharmacokinetic Analysis) Administration: Oral Result: Plasma concentrations at 2, 15, and 24 hours were 5.1, 1.8, and 0.7 μM, respectively.

[1]. Ito M, et al. Melanin-concentrating hormone 1-receptor antagonist suppresses body weight gain correlated with high receptor occupancy levels in diet-induced obesity mice. Eur J Pharmacol. 2009 Dec 10;624(1-3):77-83.

[2]. Haga Y, et al. Discovery of novel phenylpyridone derivatives as potent and selective MCH1R antagonists. Bioorg Med Chem. 2011 Jan 15;19(2):883-93.