Article Figures & Data
Figures
- Fig. 1.
The number of GPCRs targeted by approved drugs. (A) The number of GPCRs targeted by approved drugs, based on annotations of GPCR-drug interactions from each of several sources. Also included is the number of commonly listed (consensus) GPCRs and GPCRs curated in our analysis. The number of druggable GPCRs uniquely listed in each source is as follows: GtoPdb, 6; ChEMBL, 3; DrugBank, 0; and Broad Institute Drug Repurposing Hub, 24. (B) Putative primary Gα protein linkage, based on classification of GPCR signaling by GtoPdb, of the 134 curated GPCRs targeted by approved drugs. Individual GPCRs may couple to multiple G-proteins. (C and D) Venn diagrams of the GtoPdb’s list of GPCR drug targets and that of ChEMBL and DrugBank.
- Fig. 2.
The estimated proportion of genes from different gene families that are targets for approved drugs. GPCRs comprise the single largest such group. VGICs: voltage-gated ion channels; LGICs: ligand-gated ion channels.
- Fig. 3.
The number of GPCR-targeted drugs. (A) The number of approved drugs identified in GtoPdb, CHEMB, DrugBank, and the Broad repurposing hub with the consensus among the four sources and each entry combined from the four sources. (B) The percentage of approved drugs that target GPCRs in each database. (C) Venn diagram showing the relationship between identities of GPCR-related drugs listed in the GtoPdb and ChEMBL databases. (D) The types of molecules that target GPCRs, based on annotations from GtoPdb (Alexander et al., 2017).
- Fig. 4.
The 15 GPCRs with the most approved drugs and the number of such drugs listed in ChEMBL, DrugBank, and GtoPdb.
Tables
- TABLE 1
One hundred thirty-four GPCRs have FDA-approved drugs
Exceptions are those marked as follows: *, EMA approved; 1, approved in the United Kingdom by the The Medicines and Healthcare products Regulatory Agency (MHRA); 2, suramin is not listed in the FDA’s Orange Book, but is distributed by the Centers for Disease Control and is listed as an essential medicine by the World Health Organization; and #, GABBR1 and 2 combine to form a single active signaling complex that is activated by baclofen. Entries in bold in indicate GPCRs considered primary targets for the listed drug based on affinity and/or functional response (in the majority of cases, both). Entries not in bold indicate GPCRs targeted by approved drugs but for which such an interaction is not likely a primary aspect of the intended therapeutic use of such drugs.
Gene Name Example of an Approved Drug ACKR3 Plerixafor ADGRG3 Beclometasone dipropionate ADORA1 Adenosine ADORA2A Regadenoson ADORA2B Theophylline ADORA3 Nicardipine ADRA1A Oxymetazoline ADRA1B Prazosin ADRA1D Prazosin ADRA2A Apraclonidine ADRA2B Dexmedetomidine ADRA2C Dexmedetomidine ADRB1 Acebutolol ADRB2 Pindolol ADRB3 Mirabegron AGTR1 Candesartan AVPR1A Vasopressin AVPR1B Vasopressin AVPR2 Vasopressin BDKRB1 Icatibant BDKRB2 Icatibant CALCR Calcitonin CASR Etelcalcetide CCKAR Ceruletide CCKBR Pentagastrin CCR4 Plerixafor CCR5 Maraviroc CHRM1 Biperiden CHRM2 Propantheline CHRM3 Umeclidinium CHRM4 Acetylcholine CHRM5 Acetylcholine CNR1 Nabilone CNR2 Nabilone CRHR1 Corticorelin ovine triflutate CXCR4 Plerixafor CYSLTR1 Zafirlukast CYSLTR2 Zafirlukast DRD1 Dopamine DRD2 Dopamine DRD3 Dopamine DRD4 Dopamine DRD5 Dopamine EDNRA Ambrisentan EDNRB Bosentan F2R Vorapaxar FFAR1 Rosiglitazone FPR1 Cyclosporine FSHR Human follicle stimulating hormone GABBR1 # Baclofen GABBR2 # Baclofen GCGR Glucagon GHRHR Sermorelin GLP1R Lixisenatide GLP2R Teduglutide GNRHR Abarelix GPBAR1 Deoxycholic acid GPER1 Estradiol GPR143 Levodopa GPR18 Dronabinol GPR35 Bumetanide GPR55 Dronabinol GPR68 Lorazepam HCAR1 Sodium oxybate HCAR2 Acipimox 1 HCAR3 Nicotinic acid HCRTR1 Suvorexant HCRTR2 Suvorexant HRH1 Cetirizine HRH2 Betazole HRH3 Pitolisant * HRH4 Clozapine HTR1A Vilazodone HTR1B Frovatriptan HTR1D Frovatriptan HTR1E Asenapine HTR1F Eletriptan HTR2A Asenapine HTR2B Methysergide HTR2C Methysergide HTR4 Cisapride HTR5A Ergotamine HTR6 Amoxapine HTR7 Lurasidone LHCGR Choriogonadotropin alfa MC1R Corticotropin MC2R Corticotropin MC3R Corticotropin MC4R Corticotropin MC5R Corticotropin MLNR Erythromycin MRGPRX1 Chloroquine MTNR1A Ramelteon MTNR1B Tasimelteon NPY4R Niclosamide NTSR2 Levocabastine OPRD1 Naltrexone OPRK1 Anileridine OPRM1 Alfentanil OXTR Oxytocin P2RY1 Suramin 2 P2RY11 Suramin 2 P2RY12 Cangrelor P2RY13 Cangrelor P2RY2 Suramin 2 P2RY6 Suramin 2 PTGDR Treprostinil PTGDR2 Indomethacin PTGER1 Prostaglandin E1 PTGER2 Prostaglandin E2 PTGER3 Misoprostol PTGER4 Treprostinil PTGFR Latanoprost PTGIR Epoprostenol PTH1R Teriparatide PTH2R Teriparatide S1PR1 Fingolimod S1PR2 Fingolimod S1PR3 Fingolimod S1PR4 Fingolimod S1PR5 Fingolimod SCTR Secretin SMO Sonidegib SSTR1 Pasireotide SSTR2 Lanreotide SSTR3 Pasireotide SSTR4 Octreotide SSTR5 Lanreotide SUCNR1 Sodium succinate TAAR1 Dexamfetamine TACR1 Aprepitant TBXA2R Iloprost TRHR Protirelin TSHR Thyrotropin Examples of Proteins/Genes That Are Drug Targets Examples of Drugs That Target These Proteins/Genes Protein/gene category: enzymes involved in agonist synthesis Prostaglandin I2 synthase Epoprostenol Angiotensin I converting enzymes Lisinopril Dopamine beta-hydroxylase Hydralazine Coagulation factors (e.g., factor 10) Rivaroxaban Protein/gene category: enzymes involved in agonist degradation Monoamine oxidases A and B Phenelzine Catechol O-methyltransferase Entacapone Acetylcholinesterase Neostigmine Adenosine deaminase Pentostatin Dipeptidyl peptidase-4 Sitagliptin Protein/gene category: transporters of GPCR agonists Serotonin transporters Citalopram Dopamine transporters (SLC6A3) Modafinil ATP transporters (SLC25A4) Clodronic acid Protein/gene category: GPCR ligands C-C motif chemokine ligand 2 Mimosine Coagulation factor II, thrombin Argatroban Protein/gene category: regulators of second messenger signaling PDEs PDE1A-C Vinpocetine PDE4A-D Roflumilast Rho Kinases (ROCK1-2) Fasudil
Data Supplement
- Supplemental Table 1 -
The GPCRs identified as targeted by approved drugs from each source, plus a list of all human GPCRs annotated by IUPHAR, which does not include olfactory receptors
- Supplemental Table 2 -
A list of all drugs, between the different sources indicated, which target GPCRs
- Supplemental Table 3 -
Lists of all drugs, in each of the three major databases (CHEMBL, IUPHAR and DRUGBANK) indicated as targeting each GPCR
- Supplemental Table 1 -
