ALB-127158(a) is a potent and selective melanin-concentrating hormone 1 (MCH 1) receptor antagonist that may potentially treat inflammatory bowel disease (IBD).

ALB-127158(a) exhibits a high affinity for the MCH 1 receptor (7 nM), demonstrating significant selectivity against various G-protein coupled receptors (GPCRs), ion channels, and transporters, notably excluding the MCH 2 receptor. In vitro functional assays have validated ALB-127158(a) as a potent and selective antagonist of the MCH 1 receptor [1].

In a diet-induced obesity (DIO) mouse model and a high-fat diet (HFD) rat model, ALB-127158(a) effectively decreases body weight and food intake. At doses ranging from 5-15 mg/kg bid for mice and as low as 1.25 mg/kg po for rats, it significantly reduces weight, primarily by decreasing fat content, with weight loss exceeding 6% for doses above 1.25 mg/kg po in rats, and peaking at about 10% weight loss at 10 mg/kg. ALB-127158(a) is quickly absorbed after oral administration, reaching maximum plasma concentration between 1 and 3 hours in both lean and overweight/obese subjects; however, lower doses exhibit a trend towards slower absorption. The compound has an average half-life of 18 to 21 hours after a single dose, which extends to approximately 26 hours with multiple doses, achieving steady-state levels in 6 to 8 days of dosing in overweight/obese subjects.