GPR15L   Click here for help

GtoPdb Ligand ID: 10567

Synonyms: antimicrobial peptide-57 | colon-derived SUSD2 binding factor
Immunopharmacology Ligand
Compound class: Endogenous peptide in human, mouse or rat
Comment: This peptide is a product of the human C10orf99 gene. It is proposed as an agonistic ligand of the orphan GPCR, GPR15, and has been referred to as GPR15L [1]. Structurally, GPR15L is predicted to contain two intramolecular disulphide bonds, which implies a similarity to CC family cytokines.
GPR15L has also been reported as a pruritogen that is produced in the skin, which induces mast cell degranulation via activation of the Mas-related G protein-coupled receptors (MRGPRs) [2]. MRGPR-GPR15L-mediated itch and inflammation is independent of GPR15.
Species: Human
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES NCCCCC(C(=O)NC(C(=O)NC(C(=O)N1CCCC1C(=O)NC(C(=O)N1CCCC1C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)N1CCCC1C(=O)NCC(=O)NC(C(=O)NC(C(=O)N1CCCC1C(=O)NC(C(=O)NC(C(=O)O)C(C)C)CCC(=O)N)CC(C)C)C)C(C)C)C(C)C)Cc1c[nH]c2c1cccc2)CC(C)C)CCCN=C(N)N)CCC(=O)O)CCC(=O)O)CC(C)C)NC(=O)C1CSSCC(NC(=O)C(NC(=O)C(NC(=O)C(C(O)C)NC(=O)C(NC(=O)C(NC(=O)CNC(=O)C(NC(=O)C(Cc2c[nH]c3c2cccc3)NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C2CCCN2C(=O)C(NC(=O)C(NC(=O)C(CCCCN)N)CCCN=C(N)N)CCCN=C(N)N)C)CCCCN)C)CO)CCCN=C(N)N)CCCN=C(N)N)CCCN=C(N)N)CC(C)C)C(=O)NC2CSSCC(C(=O)NC(C(=O)N3C(C(=O)N1)CCC3)CCCCN)NC(=O)C(CC(C)C)NC(=O)C(CCCN=C(N)N)NC(=O)C(NC(=O)C(Cc1c[nH]cn1)NC(=O)C(NC(=O)CNC(=O)C(CCCCN)NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C1N(C(=O)C(NC(=O)C3N(C(=O)C(NC(=O)C(NC(=O)C(NC2=O)Cc2c[nH]cn2)CCCN=C(N)N)C(C)C)CCC3)CO)CCC1)CC(=O)N)CO)C(O)C)CC(=O)N)Cc1c[nH]cn1)C(C)C
Isomeric SMILES NCCCC[C@@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)NCC(=O)N[C@H](C(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)N[C@H](C(=O)N[C@H](C(=O)O)C(C)C)CCC(=O)N)CC(C)C)C)C(C)C)C(C)C)Cc1c[nH]c2c1cccc2)CC(C)C)CCCN=C(N)N)CCC(=O)O)CCC(=O)O)CC(C)C)NC(=O)[C@@H]1CSSC[C@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H]([C@H](O)C)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](Cc2c[nH]c3c2cccc3)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H]2CCCN2C(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CCCCN)N)CCCN=C(N)N)CCCN=C(N)N)C)CCCCN)C)CO)CCCN=C(N)N)CCCN=C(N)N)CCCN=C(N)N)CC(C)C)C(=O)N[C@H]2CSSC[C@@H](C(=O)N[C@H](C(=O)N3[C@H](C(=O)N1)CCC3)CCCCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H]1N(C(=O)[C@@H](NC(=O)[C@H]3N(C(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC2=O)Cc2c[nH]cn2)CCCN=C(N)N)C(C)C)CCC3)CO)CCC1)CC(=O)N)CO)[C@H](O)C)CC(=O)N)Cc1c[nH]cn1)C(C)C
InChI Key MKYBCIBFBPPBKT-QSWODBGPSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
Bioactivity Comments
GPR15L is an endogenous pruritogen that is expressed by keratinocytes in human inflammatory skin diseases. It induces itch and inflammation principally via activation of MRGPRs that are expressed on sensory neurons and mast cells [2]. These effects are independent of GPR15L's action as a GPR15 agonist.
Selectivity at GPCRs
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
GPR15 Hs Agonist Agonist 5.8 pEC50 - 1
⤷ pEC50 5.8 (EC50 1.4x10-6 M) [1]
Description: Agonist activity determined in vitro, measuring calcium response in CHO-K1 cells expressing hGPR15 and Aequorin.
MRGPRX2 Hs Agonist Agonist 5.7 pEC50 - 2
⤷ pEC50 5.7 (EC50 1.9x10-6 M) [2]
Description: Determined in a FLIPR calcium imaging assay using HEK cells heterologously expressing hMRGPRX2
MRGPRX1 Hs Agonist Agonist 4.7 pEC50 - 2
⤷ pEC50 4.7 (EC50 1.81x10-5 M) [2]
Description: Determined in a FLIPR calcium imaging assay using HEK cells heterologously expressing hMRGPRX1