GSK962040 is a first small-molecule agonist of motilin receptor with pEC50 value of 7.9 [1].
GSK962040 is discovered as a therapeutic agent for conditions associated with delayed gastric emptying. In the in vitro assay using recombinant human motilin receptor, GSK962040 shows an excellent inhibition activity against motilin receptor with pEC50 value of 7.9. GSK962040 is highly selective against motilin receptor over the human ghrelin receptor and hERG. It also has no significant activity against other receptors including 5-HT, adrenergic, dopamine, histamine and adenosine receptors. In rabbit isolated gastric antrum, GSK962040 is found to enhance the EFS-induced cholinergic contraction and cause a small muscle contraction at high concentration. GSK962040 also induces the contraction of human-isolated stomach preparations at 10μM [1, 2].
References:
[1] Westaway S M, Brown S L, Fell S C M, et al. Discovery of N-(3-Fluorophenyl)-1-[(4-([(3 S)-3-methyl-1-piperazinyl] methyl) phenyl) acetyl]-4-piperidinamine (GSK962040), the First Small Molecule Motilin Receptor Agonist Clinical Candidate. Journal of medicinal chemistry, 2009, 52(4): 1180-1189.
[2] Sanger G J, Westaway S M, Barnes A A, et al. GSK962040: a small molecule, selective motilin receptor agonist, effective as a stimulant of human and rabbit gastrointestinal motility. Neurogastroenterology & Motility, 2009, 21(6): 657-e31.