G protein-coupled receptor 35 also known asGPR35 is aG protein-coupled receptor which in humans is encoded by theGPR35gene.[5] Heightened expression of GPR35 is found in immune and gastrointestinal tissues, including thecrypts of Lieberkühn.
Although GPR35 is still considered anorphan receptor, there have been attempts to deorphanize it by identifyingendogenous molecules that can activate the receptor. All of the currently proposed ligands are eitherunselective towards GPR35, or they lack highpotency, a characteristic feature of natural ligands.[6] The following list includes the most prominent examples:
Zaprinast is currently thegold standard in thebiochemical evaluation of novel synthetic GPR35 agonists, because it remains potent in ananimal model. Most other known agonists display high selectivity towards the human GPR35orthologue. This phenomenon is well established for other GPCRs and complicates the development ofpharmaceutical drugs.[6][14][15]
Both ML145 and ML144 unfurl their antagonistic activity throughinverse agonism. They are, however, highly species-selective, and practically inactive at therodent receptor orthologues.[17]
^abYang Y, Lu JY, Wu X, Summer S, Whoriskey J, Saris C, et al. (2010). "G-protein-coupled receptor 35 is a target of the asthma drugs cromolyn disodium and nedocromil sodium".Pharmacology.86 (1). S. Karger AG:1–5.doi:10.1159/000314164.PMID20559017.S2CID9421354.
^Taniguchi Y, Tonai-Kachi H, Shinjo K (September 2006). "Zaprinast, a well-known cyclic guanosine monophosphate-specific phosphodiesterase inhibitor, is an agonist for GPR35".FEBS Letters.580 (21):5003–5008.doi:10.1016/j.febslet.2006.08.015.PMID16934253.S2CID43142927.
^Gütschow M, Schlenk M, Gäb J, Paskaleva M, Alnouri MW, Scolari S, et al. (April 2012). "Benzothiazinones: a novel class of adenosine receptor antagonists structurally unrelated to xanthine and adenine derivatives".Journal of Medicinal Chemistry.55 (7). American Chemical Society (ACS):3331–3341.doi:10.1021/jm300029s.PMID22409573.
^abHeynen-Genel S, Dahl R, Shi S, Sauer M, Hariharan S, Sergienko E, et al. (2010)."Selective GPR35 Antagonists - Probes 1 & 2".Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US).PMID21433393. Bookshelf ID NBK50703.
^Shrimpton AE, Braddock BR, Thomson LL, Stein CK, Hoo JJ (December 2004). "Molecular delineation of deletions on 2q37.3 in three cases with an Albright hereditary osteodystrophy-like phenotype".Clinical Genetics.66 (6):537–544.doi:10.1111/j.1399-0004.2004.00363.x.PMID15521982.S2CID42975740.
