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G Protein-Coupled Receptors Product Listing | Edition 1 G Protein-Coupled Receptors Product Listing | Edition 1 Opium Poppy Papaver somniferum A source of Morphine GPCR Products by Class • Class A: Rhodopsin-like • Class B: Secretin-like • Class C: Glutamate • Class F: Frizzled • GPCR Signaling Tocris Product Listing Series Contents This listing contains over 450 products, including agonists, antagonists and allosteric modulators for a wide range of G protein-coupled receptors (GPCRs). GPCRs are divided into their respective classes: Rhodopsin-like (class A), Secretin-like (class B), Glutamate (class C) and Frizzled (class F). Products for GPCR signaling are also listed. Class A: Rhodopsin-like 4 Class A9 10 Class B: Secretin-like 22 Melatonin Receptors Class A1/A2 4 Calcitonin and Related Receptors Neuropeptide Y Receptors CC Chemokine Receptors Corticotropin-releasing Factor Tachykinin Receptors CXC Chemokine Receptors Receptors Class A11 11 GIP Receptor GPCR Crystal Structures 5 Free Fatty Acid Receptors Glucagon Receptor Class A2 6 Hydroxycarboxylic Acid Receptors Glucagon-Like Peptide Receptors Estrogen (GPER) Receptors Class A11/12 11 PACAP Receptor Class A3 6 Purinergic Receptors Parathyroid Hormone Receptors Angiotensin Receptors Class A12 12 Secretin Receptor Apelin Receptors Platelet-activating Factor Receptor VIP Receptors Bradykinin Receptors Class A13 12 Class C: Glutamate 24 Class A4 6 Cannabinoid Receptors Calcium-sensing Receptor Opioid Receptors Melanocortin Receptors GABA Receptors Neuropeptide W/B Receptors B Sphingosine-1-phosphate Receptors Glutamate (Metabotropic) Receptors Somatostatin Receptors Class A13/15 13 GPCR Allostery 27 Class A5 7 Lysophosphatidic Acid Receptors Galanin Receptors Class A14 14 Class F: Frizzled 28 Kisspeptin Receptors Prostanoid Receptors Smoothened Receptor Leukotriene Receptors Thromboxane (TP) Receptors Melanin-concentrating Hormone GPCR Signaling 29 Class A15 14 (MCH) Receptors GPR35 Adenylyl Cyclase Urotensin-II Receptors Protease-activated Receptors cAMP Class A6 8 G Protein (Heterotrimeric) Class A17 15 Cholecystokinin Receptors GRK Adrenergic Receptors GnRH Receptor IP Receptor Dopamine Receptors 3 GPR103 Phospholipases Trace Amine 1 Receptor Orexin Receptors Oxytocin Receptor Class A17/18 17 Bias Signaling 30 Histamine Receptors Vasopressin Receptors References and Further Reading 31 Class A17/19 18 Class A7 9 Bombesin Receptors 5-HT Receptors Endothelin Receptors Class A18 19 Ghrelin Receptor Adenosine Receptors Motilin Receptor Acetylcholine Muscarinic Receptors Neuromedin U Receptors Other GPCRs 21 Neurotensin Receptors Neuropeptide FF/AF Receptors Thyrotropin-Releasing Hormone Orphan GPCRs Receptors Sensory Neuron-specific Receptors Class A8 10 DREADD Ligands 21 Formyl Peptide Receptors 2 | GPCR ReSeaRCh Introduction GPCRs are transmembrane receptors that mediate signal transduction from the cytosol to the cell interior. There are approximately 850 known GPCRs, which make up the largest receptor superfamily. GPCRs can be classified according to their structural and functional relationship, as represented by the ‘GPCR Tree’. A Representation of the GPCR Tree Featuring Genes of GPCRs Targeted by Tocris Products ADRA1 ADRB3 HTR7 ADRB1 HTR2 S1PR LPAR HTR5 ADRB2 CNR1 CNR2 HTR1 Class A – Rhodopsin-like ADRA2 DRD5 DRD1 MCR CHRM1 HTR6 CHRM1 CHRM1 CHRM1 ADORA2B ADORA2A CHRM1 HTR4 MLNR DRD2 TAR1 ADORA3 ADORA1 DRD4 DRD3 TBXA2R PTGFR HRH4 HRH3 EDNRB BRS3 GRPR OXTR PTGER1 EDNRA HRH2 HRH1 NMBR AVPR GNR PTGIR CCKAR HCRTR1 CCKBR PAR HCRTR CYSLTR NPFFR TACR2 GPR17 GPR35 GPR103 PTAFR EBI2 TRHR TACR1 P2YR NMUR NPYR TACR3 GPR55 MTLR NTSR MRGX1 (SNSR1) GHSR BLTR FPR1 UR2R MCHR GHRHR Class B – Secretin-like AGTRL1 GALR BDKBR SSTR SCTR CXCR GPR54 AGTR1 GPR7 CALCR VIPR CCR OPRL CRH1 PACAPR OPRK CRH1 GLPR OPRM CASR PTHR GIPR OPRD GABBR GRM5 GCGR GRM1 SMOH GRM2 GRM3 Class F – Frizzled GRM6 GRM4 GRM7 GRM8 Class C – Glutamate adapted from Raymond et al (2013) Nat.Rev.Drug Discov. 12 25. GPCR Tree Gene Abbreviations ADORA, adenosine receptor; ADR, adrenergic receptor; AGTR, angiotensin receptor; AGTRL1, apelin receptor; AVPR, vasopressin receptor; BDKRB, bradykinin receptor; BRS3, bombesin-like receptor 3; CALCR, calcitonin receptor; CASR, calcium sensing receptor; CCKR, cholecystokinin receptor; CCR, CC chemokine receptor; CHRM, acetylcholine muscarinic receptor; CNR, cannabinoid receptor; CRHR, corticotropin-releasing factor receptor; CXCR, CXC chemokine receptor; CYSLTR, cysteinyl leukotriene receptor; DRD, dopamine receptor; EBI2, eBV-induced G-protein coupled receptor 2; S1PR, sphingosine-1-phosphate receptor; EDNR, endothelin receptor; FPR, formyl peptide receptor; GABBR, GaBaB receptor; GALR, galanin receptor; GCGR, glucagon receptor; GHSR, ghrelin receptor; GIPR, GIP receptor; GLPR, glucagon-like receptor; GNRHR, gonadotropin-releasing hormone receptor; GPR, G-protein coupled receptor; GRM, glutamate receptor metabotropic; GRPR, gastrin-releasing peptide receptor; HCRTR, orexin receptor; HRH, histamine receptor; HTR, 5-hT receptor; LPAR, lysophosphatidic acid receptor; MCR, melanocortin receptor; MCHR, melanin-concentrating hormone receptor; MRGX1 (SNSR1), sensory neuron-specific receptor;MLNR , motilin receptor; MLNR, melatonin receptor; NMBR, neuromedin receptor; NMUR, neuromedin U receptor; NPFFR, neuropeptide FF receptor; NPYR, neuropeptide Y receptor; NTSR, neurotensin receptor; OPR, opioid receptor, OXTR, oxytocin receptor; P2YR, purinergic receptor; PACAPR, pituitary adenylate cyclase-activating polypeptide; PAR, protease-activated receptor; PTAFR, platelet-activating factor receptor; PTGER, prostaglandin e2 receptor; PTGFR, prostaglandin F2 receptor; PTGIR; prostacyclin receptor; PTHR, parathyroid hormone receptor; SCTR, secretin receptor; SMOH, smoothened receptor; SSTR, somatostatin receptor; TACR; tachykinin receptor; TAR1, trace amine 1 receptor; TBXA2R, thromboxane a2 receptor; TRHR, thyrotropin-releasing hormone receptor; UR2R, urotensin receptor; VIPR, vasoactive intestinal peptide tocris.com | 3 Tocris Product Listing Series Class a: Rhodopsin-like The Rhodopsin-like receptors are the largest class within the GPCR superfamily, being characterized by certain conserved amino acid residues in their transmembrane helices. Class A receptors have a wide variety of ligands including, neurotransmitters, peptides, glycoproteins, steroid hormones and lipids. Category Cat. No. Product Name Description Unit Size Class A1/A2: CC Chemokine Receptors Antagonists 3129 BMS CCR2 22 high affinity, potent CCR2 antagonist 1 mg 10 mg 50 mg 2595 J 113863 Potent CCR1 antagonist 1 mg 10 mg 50 mg 5176 JNJ 27141491 Potent and selective human CCR2 antagonist 10 mg 50 mg 3756 Maraviroc Selective CCR5 antagonist 10 mg 50 mg 2089 RS 102895 CCR2b antagonist 10 mg 50 mg 2517 RS 504393 highly selective CCR2 antagonist 10 mg 3650 SB 328437 Potent and selective CCR3 antagonist 10 mg 50 mg CXC Chemokine Receptors Agonists 4780 VUF 11207 Potent CXCR7 (aCKR3) agonist 10 mg 50 mg 5668 VUF 11222 high affinity non-peptide CXCR3 agonist 10 mg 50 mg Antagonists 3299 aMD 3100 highly selective CXCR4 antagonist 10 mg 50 mg 4179 aMD 3465 Potent, selective CXCR4 antagonist 10 mg 50 mg 4487 (±)-aMG 487 CXCR3 antagonist; inhibits cell migration and metastasis 10 mg 50 mg 5130 CTCe 9908 CXCR4 antagonist; antitumor 1 mg 4596 IT1t Potent CXCR4 antagonist 10 mg 50 mg CXCR4 in Complex with IT1t Crystal Structure of the CXCR4 Homodimer in Complex with the CXCR4 Antagonist IT1t CXCR4 – IT1t 4596 H1 – Doxepin 0508 Cat. No. 4596 O NH N S N N N S • IT1t binds to part of the binding cavity of CXCR4 and interacts with side chains from helices I, II, III and VII • IT1tB2- isA da rpotentenerg CXCR4ic – ICI antagonist118,551 (IC 0821 = 1.1 nM) Image adapted from the RSCB PDB (www.rcsb.org) of PDB ID: 3Oe9 50 CRF1R – CP-376395 3212 Wu et al (2010) Science 330 1066. PMID 20929726. • The compound is orally available 4 | N O O N H N HO H A2A – ZM 241385 1036 MGLUR1 – LY 341495 1209 OH NH2 O O N N N N N N H2N H CO2H OH O D3 – Eticlopride 1847 HO O N N H O Cl GPCR ReSeaRCh Class a: Rhodopsin-like – continued GPCR Crystal Structures Crystallography refers to the study of atomic and molecular structure. The elucidation of molecular structures of membrane proteins such as GPCRs has proven problematic, and only a small fraction of known GPCRs have been solved to date. GPCR crystal structures are invaluable for structure-based drug discovery approaches. GPCR Crystal Structures and Drug Discovery: The solving of GPCR crystal structures has been notoriously difficult, due to their flexible conformations. For their structure to be solved GPCRs need to be embedded in a membrane-like environment to maintain their structural integrity. This was difficult to achieve until the last decade, when certain mutations were found to increase GPCR stability and expression levels, while stabilization antibodies can also enhance GPCR stability. The first GPCR structure to be crystallized was the Rhodopsin receptor in 2000, and receptor stabilization techniques resulted in the discovery of the adenosine a2a receptor and adrenergic β1 and β2 receptors in 2008. To date 26 GPCR structures have been solved (see table below). GPCR crystal structures could prove to be essential for next generation drug discovery. These structures can be utilized by automated computational screens for the identification of novel ligands and chemotypes, which could produce lead compounds for the synthesis of next generation drugs and enhanced therapeutics. GPCR Species Ligand PDB-ID Reference acetylcholine Muscarinic M2 Receptor human
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