Orphan GPCR Agonist

Tryptophan-cholic acid (Trp-CA) is a microbial amino acid-conjugated bile acid that acts as an endogenous ligand and agonist (EC₅₀=9.6 μM) for the orphan G protein-coupled receptor (GPCR) MRGPRE (Mas-related G protein-coupled receptor family member E). Tryptophan-cholic acid is orally effective but has poor oral absorption and does not cross the blood-brain barrier. Tryptophan-cholic acid promotes the secretion of glucagon-like peptide GLP-1, thereby improving glucose tolerance in diabetic mice. Tryptophan-cholic acid improves glucose tolerance, promotes insulin secretion, and alleviates high-fat diet-induced hepatic steatosis without causing pruritus side effects. Tryptophan-cholic acid is primarily used in research on type 2 diabetes (T2D).

GPR3 agonist-2(compound 32) is a potent full agonist of G protein-coupled receptor 3, with the IC₅₀of 260 nM.

2-(Phenylethynyl)-ATP (ammonium) is a selective and potent GPR17 agonist with an EC₅₀ of 35 pM. 2-(Phenylethynyl)-ATP (ammonium) also shows weak activation of P2Y Receptor. 2-(Phenylethynyl)-ATP (ammonium) can be used for the research of neurological disease.

PT-91 is an agonist of GPR27. PT-91 exhibits high metabolic stability and brain exposure in mice.

CID 1375606 is a surrogate agonist of orphan G protein-coupled receptor GPR27.

PSB-1737 is a human-selective GPR17 agonist with an EC₅₀ for human GPR17 of 270 nM, and its activity on murine GPR17 is relatively weak (EC₅₀ > 10 μM). PSB-1737 shows no significant inhibition at the glycine binding site of NMDA receptors, and has no significant agonistic or antagonistic activity on P2Y receptor subtypes. PSB-1737 can be used in demyelinating diseases (such as multiple sclerosis) or inflammatory-related anemia.

GPR34 agonist 1 (Compound M1), a lysophosphatidylserine analogue, is an efficient GPR34 agonist.