Evolution of physicochemical properties of melanin concentrating hormone receptor 1 (MCHr1) antagonists.
One pharmacological principle for the treatment of obesity is blockade of the melanin concentrating hormone receptor 1 (MCHr1), which in rodents has been shown to be strongly associated with food intake and energy expenditure. However, discovery of safe and efficacious MCHr1 antagonists has proved to be complex. So far, six compounds have been progressed into clinical trials, but clinical validation of the concept is still lacking. An account of discovery of the three most recent clinical candidates targeting the MCHr1 receptor is given, with an emphasis on their physicochemical properties.
Cardiovascular and Metabolic Diseases, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Pepparedsleden 1, Mölndal 431 83, Sweden. Electronic address: anders.m.johansson@astrazeneca.com.
Anders
A
Johansson
D000818:Animals; D004734:Energy Metabolism; D005247:Feeding Behavior / Q000187:drug effects; D006801:Humans; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors*
C103263:MCHR1 protein, human; D017481:Receptors, Somatostatin
CNS; MCHr1; Melanin concentrating hormone receptor 1; Physicochemical properties; Target engagement