GPCR Target Panels
Functional GPCR assays grouped by therapeutic area and safety
ChanTest’s GPCR screening portfolio comprises over 125 targets, and includes receptors from all major GPCR classes. This portfolio has been organized into GPCR Target Panels based on current scientific findings, and can help guide automated screens by therapeutic area for profiling and safety assessment. Check back regularly for an updated listing of available targets.
Transient GPCR activation regulates heart rate and contractile strength to accommodate changes in circulatory requirements. In the failing heart, chronic activation of GPCRs, such as under adrenergic α1A, serotonergic 5-HT2B, endothelin ETA, and angiotensin AT1, leads to pathological remodeling (alterations in ion channel expression, tissue composition, and chamber size) that degrade heart performance. Similarly, under pathological inflammatory conditions activation of GPCRs (e.g., A3 adenosine and P2Y11 receptors) contributes to heart failure, acute myocardial infaction, and valvular disease. The muscarinic acetylcholine M2 receptor, responsible for vagal inhibition of heart rate, is included for potential off-target effects of non-selective muscarinic antagonists on heart rate.
| Target | Receptor | Validation* |
|---|---|---|
| 5HT2B | Serotonin | CA |
| 5HT2b | Serotonin | BND, cAMP |
| A1 | Adenosine | cAMP |
| A3 | Adenosine | cAMP |
| Alpha1a | Adrenergic | CA |
| Alpha2a | Adrenergic | BND, cAMP |
| AT1 | Angiotensin | CA |
| ETA | Endothelin | CA |
| m2 | Muscarinic | BND, cAMP |
CA: calcium - cAMP: cyclic AMP - CNG: cell membrane depolarization - BND: binding | ||
GPCRs that are potential targets for treating cancer include free fatty acid receptors (GPR40), endothelin receptors (ETA and ETB), adenosine receptors (A3), protease-activated receptors (PAR1 and PAR2), and lysophosphatidic acid receptors (LPA1 and S1P1) expressed in cancer cells, regulate the proliferation, migration or survival of tumor and/or supporting cells.
| Target | Receptor | Validation* |
|---|---|---|
| A3 | Adenosine | cAMP |
| AT1 | Angiotensin | CA |
| BB2 | Bombesin | CA |
| EDG1 (S1P1) | Lysophospholipid | BND, cAMP |
| ETA | Endothelin | CA |
| ETB | Endothelin | CA |
| FPRL1 | Formylpeptide | BND, CA |
| FPRL1 | Formylpeptide | CA |
| GPR40 | Free Fatty Acid | CA |
| LPA1 | Lysophosphatidic Acid | BND, cAMP |
| MC1 | Melanocortin | cAMP |
| PAR1 | Protease-Activated | CA |
| PAR2 | Protease-Activated | BND, CA |
| SSTR5 | Somatostatin | BND, CA |
CA: calcium - cAMP: cyclic AMP - CNG: cell membrane depolarization - BND: binding | ||
GPCR targets for treatment of hypertension include α2A adrenoceptors that are responsible for inhibition of vasoconstriction subsequent to norepinephrine release. Also, antagonists against either AT1 angiotensin receptors or ETA endothelin receptors block the vasoconstrictive actions of neuropeptides. Therapeutic targets for vascular inflammation, atherosclerosis, and thrombosis include metabotropic purinergic receptors (P2Y12 and P2Y6) and thrombin receptors (PAR1 and PAR4) that promote platelet aggregation, thrombus formation, vascular inflammation. Antagonists against the chemokine receptor CCR2b inhibit vascular inflammation by disrupting leucocyte migration to the inflammatory site. Activation of the lysophospholipid recptor S1P1 promotes release of anti-atherosclerotic nitric oxide in the endothelium.
| Target | Receptor | Validation* |
|---|---|---|
| A2 | Thromboxane | BND |
| Alpha1a | Adrenergic | CA |
| Alpha2a | Adrenergic | BND, cAMP |
| AT1 | Angiotensin | CA |
| CCR2B | Chemokine | cAMP |
| EDG1 (S1P1) | Lysophospholipid | BND, cAMP |
| ETA | Endothelin | CA |
| ETB | Endothelin | CA |
| P2Y1 | Purinergic | CA |
| P2Y12 | Purinergic | CA |
| P2Y6 | Purinergic | CA |
| PAR1 | Protease-Activated | CA |
| PAR4 | Protease-Activated | CA |
| V1a | Vasopressin | BND, CA |
| V2 | Vasopressin | BND, CA |
| β2 | Adrenergic | cAMP |
CA: calcium - cAMP: cyclic AMP - CNG: cell membrane depolarization - BND: binding | ||
Smooth muscle contraction in the prostate is controlled by adrenoreceptors, α1A and α1D, whereas M3 muscarinic receptors stimulate bladder smooth muscle. Thus, α1-selective blockers are effective in treating urinary retention in benign prostatic hyperplasia and M3-antagonists are used in treating overactive bladder. Bladder relaxation via β3 adrenoceptor agonists, also has potential in treatment of overactive bladder. Bombesin BB2 receptors are potential targets for treatment of psychogenic erectile dysfunction that arises at the spinal level.
| Target | Receptor | Validation* |
|---|---|---|
| Alpha1a | Adrenergic | CA |
| BB2 | Bombesin | CA |
| m2 | Muscarinic | BND, cAMP |
| m3 | Acetylcholine | BND, CA |
| V2 | Vasopressin | BND, CA |
CA: calcium - cAMP: cyclic AMP - CNG: cell membrane depolarization - BND: binding | ||
GPCRs are important drug targets in obesity, diabetes, and inflammatory disorders of the gastro-intestinal tract. Food intake, for instance, is regulated by GPCRs in central appetite control (e.g., histamine H1, serotonin 5-HT2C and 5-HT6, cannabinoid CB1, cholecystokinin CCKA and CCKB, galanin receptors, orexin OX1 and OX2, oxytocin OTR, and RFamide peptide GPR103), and in peripheral metabolic homeostasis (e.g., free fatty acid receptors GPR119, GPR120, and GPR41, GPR40). Therapeutic targets for diabetes that include GPCRs that modulate insulin secretion and glucose homeostasis: free fatty acid receptors (GPR119, GPR40, and GPR41), adenosine A1, angiotensin AT1, and gastric inhibitory peptide receptor GIP. GPCR targets for treatment of inflammatory disorders such as irritable or inflammatory bowel disease include adrenergic α2A, muscarinic M3, free fatty acid GPR43, cholecystokinin CCKA, and proteinase-activated PAR2.
| Target | Receptor | Validation* |
|---|---|---|
| 5-HT6 | Serotonin | BND |
| 5HT2c | Serotonin | BND |
| A1 | Adenosine | cAMP |
| Alpha2a | Adrenergic | BND, cAMP |
| AT1 | Angiotensin | CA |
| CB1 | Cannabinoid | BND, cAMP |
| CB1 | Cannabinoid | BND, cAMP |
| CCKA | Cholecystokinin | CA |
| CCKB | Cholecystokinin | CA |
| GIPR | Gastric Inhibitory Polypeptide | BND, cAMP |
| GPR103 | RFamide peptide | CA |
| GPR119 | Free Fatty Acid | cAMP |
| GPR120 | Free Fatty Acid | CA |
| GPR40 | Free Fatty Acid | CA |
| GPR41 | Free Fatty Acid | CA |
| GPR43 | Free Fatty Acid | CA |
| H1 | Histamine | CA |
| Kappa | Opioid | cAMP |
| m3 | Acetylcholine | BND, CA |
| ORL1 | Opioid | cAMP |
| OTR | Oxytocin | CA |
| OX1 | Orexin | BND, CA |
| OX2 | Orexin | BND, CA |
| PAR2 | Protease-Activated | BND, CA |
CA: calcium - cAMP: cyclic AMP - CNG: cell membrane depolarization - BND: binding | ||
Neurodegeneration-Stroke Target Panel
Several GPCRs expressed in the brain are therapeutic targets for treatment of neurodegenerative conditions such as Alzheimer’s and Parkinson’s diseases, including muscarinic cholinergic M1, M2, and M4; serotonin 5-HT1A, 5-HT2C, and 5-HT6 receptors. Neuroprotection in ischemic (i.e. stroke) or traumatic brain injury can be modulated by GPCRs including cannabinoid CB2, prostanoid TP, adenosine A3, purinergic P2Y1, and angiotensin AT1 receptors.
| Target | Receptor | Validation* |
|---|---|---|
| 5-HT6 | Serotonin | BND |
| 5HT1A | Serotonin | BND, cAMP |
| 5HT2c | Serotonin | BND |
| A2 | Thromboxane | BND |
| A3 | Adenosine | cAMP |
| AT1 | Angiotensin | CA |
| CB2 | Cannabinoid | BND, cAMP |
| CB2 | Cannabinoid | cAMP |
| FPRL1 | Formylpeptide | BND, CA |
| m1 | Acetylcholine | BND, CA |
| m2 | Muscarinic | BND, cAMP |
| m3 | Muscarinic | BND, CA |
| NTSR1 | Neurotensin | CA |
| P2Y1 | Purinergic | CA |
| PAR1 | Protease-Activated | CA |
CA: calcium - cAMP: cyclic AMP - CNG: cell membrane depolarization - BND: binding | ||
Pain-Inflammation Target Panel
G-protein coupled receptors that are potential targets for centrally-mediated pain suppression include neurotransmission modulators (adrenergic α2A and α2C, cannabinoid CB1, purinergic P2Y12, opioid δ, κ, μ, opioid receptor-like ORL1, and somatostatin (SST4). Targets for pain suppression in sensory neurons include Mas-related receptors (MRGPRX1 and MRGPRX2) and the prokineticin receptor (PKR2). The GPCR panel (Table 2) also includes several receptors expressed peripherally that modulate inflammatory response: cannabinoid CB2, lysophospholipid S1P1, purinergic P2Y11 and P2Y6, bombesin BB2, and protease-activated PAR2.
| Target | Receptor | Validation* |
|---|---|---|
| A1 | Adenosine | cAMP |
| A3 | Adenosine | cAMP |
| Alpha2a | Adrenergic | BND, cAMP |
| Alpha2c | Adrenergic | BND, cAMP |
| BB2 | Bombesin | CA |
| CB1 | Cannabinoid | BND, cAMP |
| CB1 | Cannabinoid | BND, cAMP |
| CB2 | Cannabinoid | BND, cAMP |
| CB2 | Cannabinoid | cAMP |
| Delta | Opioid | cAMP |
| ETA | Endothelin | CA |
| H1 | Histamine | CA |
| Kappa | Opioid | cAMP |
| LPA1 | Lysophosphatidic Acid | BND, cAMP |
| Mrg-X1 | Mas-related | CA |
| Mrg-X2 | Mrg-X2 | CA |
| Mu | Opioid | cAMP |
| NTSR1 | Neurotensin | CA |
| ORL1 | Opioid | cAMP |
| P2Y11 | Purinergic | CA |
| P2Y12 | Purinergic | CA |
| P2Y6 | Purinergic | CA |
| PAR2 | Protease-Activated | BND, CA |
| PKR2 | Prokineticin | CA |
| SSTR4 | Somatostatin | BND, CA |
CA: calcium - cAMP: cyclic AMP - CNG: cell membrane depolarization - BND: binding | ||
Seizure-Convulsion Target Panel
Available GPCRs that are anti-seizure targets include α2A adrenoceptors that serve as presynaptic autoreceptors to inhibit norepinephrine release. Selective α2A agonists have anticonvulsant action in animal models.
| Target | Receptor | Validation* |
|---|---|---|
| Alpha2a | Adrenergic | BND, cAMP |
| SSTR4 | Somatostatin | BND, CA |
CA: calcium - cAMP: cyclic AMP - CNG: cell membrane depolarization - BND: binding | ||
Psychiatric Disorder Target Panel
G-protein coupled receptors expressed in the brain are targets for treatment of several neurological conditions. In schizophrenia, muscarinic M1 agonists, serotonergic 5-HT6 antagonists, and adrenergic α2C antagonists have the potential to improve cognition deficits, whereas muscarinic M4 agonists and serotonergic 5-HT2C agonists inhibit the dopaminergic neuronal hyperactivity thought to cause hallucinations and delusions. Potential targets for anxiety include serotoninergic receptors (5-HT1A and 5-HT6) and neuropeptide receptors (CCKB and V1B). Potential or established targets for depression include adrenergic α2C receptors, serotonergic 5-HT1A and 5-HT2C receptors, and neuropeptide V1B receptors.
| Target | Receptor | Validation* |
|---|---|---|
| 5-HT6 | Serotonin | BND |
| 5HT1A | Serotonin | BND, cAMP |
| 5HT2c | Serotonin | BND |
| Alpha2c | Adrenergic | BND, cAMP |
| BB2 | Bombesin | CA |
| CCKB | Cholecystokinin | CA |
| m1 | Acetylcholine | BND, CA |
| m4 | Muscarinic | BND, cAMP |
| ORL1 | Opioid | cAMP |
| V1b | Vasopressin | BND, CA |
CA: calcium - cAMP: cyclic AMP - CNG: cell membrane depolarization - BND: binding | ||
Pulmonary-Respiratory Target Panel
G-protein coupled receptors are major components in regulation of airway tone that can increase airway resistance via contraction of bronchial smooth muscle (M2 and M3 muscarinic acetylcholine receptors) or decrease resistance via muscle relaxation (β2 adrenergic receptors). Therefore, muscarinic antagonists and β-adrenergic agonists are major therapeutic targets in treatment of asthma and chronic obstructive pulmonary disese (COPD). Less prominently, activation of A1 adenosine receptors also contributes to bronchoconstriction and A1 antagonists have been used to promote bronchodilation.
| Target | Receptor | Validation* |
|---|---|---|
| 5HT2B | Serotonin | CA |
| 5HT2b | Serotonin | BND, cAMP |
| A1 | Adenosine | cAMP |
| ETA | Endothelin | CA |
| ETB | Endothelin | CA |
| m1 | Acetylcholine | BND, CA |
| m2 | Muscarinic | BND, cAMP |
| m3 | Acetylcholine | BND, CA |
| β2 | Adrenergic | cAMP |
CA: calcium - cAMP: cyclic AMP - CNG: cell membrane depolarization - BND: binding | ||
Download: GPCR targets and assay readout pdf.
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