Orphan 7-TM Receptors

Orphan 7-TM receptors (orphan GPCRs) are receptors for which there are no defined ligands. Traditionally, receptors are characterized by specific ligands and stimuli; the search for ligands of orphan receptors is therefore akin to reverse-engineering this process.

Products
Background
Gene Data

Agonists

Cat No Product Name / Activity
6304 BigLEN (mouse)
GPR171 agonist
6306 BigLEN (rat)
Potent GPR171 agonist
6277 7α,25-Dihydroxycholesterol
Highly potent GPR183 (EBI2) agonist
0504 Diphenyleneiodonium chloride
GPR3 agonist; also inhibits NOS and NADPH oxidases
5666 JNJ 63533054
Potent and selective GPR139 agonist
4074 PF9 tetrasodium salt
Potent GPR17 agonist
5151 Prosaptide TX14(A)
Potent GPR37 and GPR37L1 agonist
5355 TC-G 1008
Potent and selective GPR39 agonist
4255 TC-O 9311
Potent and selective GPR139 agonist

Antagonists

Cat No Product Name / Activity
5203 NIBR 189
Potent and selective EBI2 (GPR183) receptor antagonist

Modulators

Cat No Product Name / Activity
5722 Ogerin
Selective positive allosteric modulator at GPR68

Ligands

Cat No Product Name / Activity
4402 26RFa
Ligand of GPR103; orexigenic neuropeptide

Orphan 7-TM receptors (orphan GPCRs) are receptors for which there are no defined ligands. Traditionally, receptors are characterized by specific ligands and stimuli; the search for ligands of orphan receptors is akin to reverse-engineering this process, since the receptors have been identified but they are responding to as-yet unidentified endogenous ligands. There are approximately 150 orphan 7-TM receptors, subdivided into three classes: Class A, Class B and Class C. Orphan G-protein coupled receptors are usually identified by number (e.g. GPR35, GPR139) and as they are 'de-orphanized' (by discovery of ligand), they sometimes maintain this prefix (e.g. GPR55). The histamine H4 (GPRv53) and GABAB receptors are further examples of de-orphanized receptors which have recently expanded existing GPCR families.

Screening of putative ligands, reverse pharmacology and the prediction of candidate ligands using structural similarities are three of the methods currently used to isolate ligands for these orphan receptors. Putative ligands for some of the orphan receptors include kynurenic acid (GPR35) and motilin (GPR38). Generation of synthetic ligands for orphan receptors also holds great therapeutic potential: the melanin-concentrating hormone receptor is one such example of a de-orphanized receptor that has developed into a target for obesity, anxiety and depression.There has been great interest in the function of orphan receptors; elucidating the cellular interactions involving them may lead to a greater understanding of existing processes.

Orphan 7-TM Receptor Gene Data

Gene Species Gene Symbol Gene Accession No. Protein Accession No.
GPR35 Human GPR35 NM_001195382 Q9HC97
Mouse Gpr35 NM_022320 Q9ES90
Rat Gpr35 NM_001037359 Q33BM1
GPR139 Human GPR139 NM_001002911 Q6DWJ6
Mouse Gpr139 NM_001024138 Q80UC8
Rat Gpr139 NM_001024241 P0C0W8