G Protein Coupled Receptors (GPCRs) perceive many extracellular signals and transduce them to heterotrimeric G proteins, which further transduce these signals intracellular to appropriate downstream effectors and thereby play an important role in various signaling pathways. G proteins are specialized proteins with the ability to bind the nucleotides guanosine triphosphate (GTP) and guanosine diphosphate (GDP). In unstimulated cells, the state of G alpha is defined by its interaction with GDP, G beta-gamma, and a GPCR. Upon receptor stimulation by a ligand, G alpha dissociates from the receptor and G beta-gamma, and GTP is exchanged for the bound GDP, which leads to G alpha activation. G alpha then goes on to activate other molecules in the cell. These effects include activating the MAPK and PI3K pathways, as well as inhibition of the Na+/H+ exchanger in the plasma membrane, and the lowering of intracellular Ca2+ levels.

Most human GPCRs can be grouped into five main families named; Glutamate, Rhodopsin, Adhesion, Frizzled/Taste2, and Secretin, forming the GRAFS classification system.

A series of studies showed that aberrant GPCR Signaling including those for GPCR-PCa, PSGR2, CaSR, GPR30, and GPR39 are associated with tumorigenesis or metastasis, thus interfering with these receptors and their downstream targets might provide an opportunity for the development of new strategies for cancer diagnosis, prevention and treatment. At present, modulators of GPCRs form a key area for the pharmaceutical industry, representing approximately 27% of all FDA-approved drugs.

References:
[1] Moreira IS. Biochim Biophys Acta. 2014 Jan;1840(1):16-33.
[2] Tuteja N. Plant Signal Behav. 2009 Oct;4(10):942-7.
[3] Williams C, et al. Methods Mol Biol. 2009;552:39-50.
[4] Schiöth HB, et al. Gen Comp Endocrinol. 2005 May 15;142(1-2):94-101.
[5] Wu J, et al. Cancer Genomics Proteomics. 2012 Jan;9(1):37-50.


Anti-infection >
Arenavirus Bacterial CMV Enterovirus Filovirus Fungal HBV HCV HIV HSV Influenza Virus Parasite Reverse Transcriptase RSV SARS-CoV
Antibody-drug Conjugate >
ADC Cytotoxin ADC Linker Drug-Linker Conjugates for ADC PROTAC-linker Conjugate for PAC
Apoptosis >
Apoptosis Bcl-2 Family c-Myc Caspase DAPK Ferroptosis IAP MDM-2/p53 PKD RIP kinase Survivin Thymidylate Synthase TNF Receptor
Autophagy >
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15-PGDH 5 alpha Reductase 5-Lipoxygenase Acetyl-CoA Carboxylase Acyltransferase Adenosine Deaminase Adenosine Kinase Aldehyde Dehydrogenase (ALDH) Aldose Reductase Aminopeptidase Angiotensin-converting Enzyme (ACE) ATGL ATP Citrate Lyase Carbonic Anhydrase Carboxypeptidase Cathepsin CETP COMT Cytochrome P450 Dipeptidyl Peptidase Dopamine β-hydroxylase E1/E2/E3 Enzyme Elastase Enolase FAAH FABP Factor Xa Farnesyl Transferase Fatty Acid Synthase (FAS) FXR Glucokinase GSNOR Gutathione S-transferase HCV Protease Hexokinase HIF/HIF Prolyl-Hydroxylase HIV Integrase HIV Protease HMG-CoA Reductase (HMGCR) HSP Indoleamine 2,3-Dioxygenase (IDO) Isocitrate Dehydrogenase (IDH) Lactate Dehydrogenase LXR MAGL Mineralocorticoid Receptor Mitochondrial Metabolism MMP Nampt NEDD8-activating Enzyme Neprilysin PAI-1 PDHK PGC-1α Phosphatase Phosphodiesterase (PDE) Phospholipase Procollagen C Proteinase Proteasome Pyruvate Kinase RAR/RXR Renin ROR Ser/Thr Protease SGK Stearoyl-CoA Desaturase (SCD) Thrombin Tryptophan Hydroxylase Tyrosinase Xanthine Oxidase
Neuronal Signaling >
5-HT Receptor AChE Adenosine Kinase Amyloid-β Beta-secretase CaMK CGRP Receptor COMT Dopamine Receptor Dopamine Transporter FAAH GABA Receptor GlyT iGluR Imidazoline Receptor mAChR Melatonin Receptor Monoamine Oxidase nAChR Neurokinin Receptor Opioid Receptor Serotonin Transporter γ-secretase
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Akt AMPK ATM/ATR DNA-PK GSK-3 MELK mTOR PDK-1 PI3K PI4K PIKfyve PTEN
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Atropine sulfate

Atropine sulfate is a competitive muscarinic acetylcholine receptor antagonist.IC50 value:Target: mAChRAtropine is a naturally occurring tropane alkaloid extracted from deadly nightshade (Atropa belladonna), Jimson weed (Datura stramonium), mandrake (Mandragora officinarum) and other plants of the family Solanaceae. Atropine is a competitive antagonist of the muscarinic acetylcholine receptors (acetylcholine being the main neurotransmitter used by the parasympathetic nervous system). Atropine dilates the pupils, increases heart rate, and reduces salivation and other secretions [1].

  • CAS Number: 55-48-1
  • MF: C17H23NO3.1/2H2O4S
  • MW: 338.41
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: 429.8ºC at 760 mmHg
  • Melting Point: 189-192 °C (A)(lit.)
  • Flash Point: 213.7ºC

N-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-[2-(2H-tetrazol-5-yl)pyridin-4-yl]pyrimidin-4-yl]-5-methyl-pyridine-2-sulfonamide

Clazosentan (Ro 61-1790) is a selective endothelin A (ETA) receptor antagonist. Clazosentan inhibits ET-1-mediated vasoconstriction. Clazosentan prevents cerebral vasospasm, vasospasm-related cerebral infarction[1][5].

  • CAS Number: 180384-56-9
  • MF: C25H23N9O6S
  • MW: 577.57200
  • Catalog: Endothelin Receptor
  • Density: 1.485g/cm3
  • Boiling Point: 754.5ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 410.1ºC

L-693,403 maleate

L-693403 maleate is a high affinity and selective σ ligand. L-693403 maleate has the potential for physiological disease research[1].

  • CAS Number: 207455-21-8
  • MF: C24H27NO4
  • MW: 393.48
  • Catalog: Sigma Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

LY377604

LY377604 is a human β3-adrenergic receptor agonist with an EC50 of 2.4 nM and also a β1- and β2-adrenergic receptor antagonist.

  • CAS Number: 204592-94-9
  • MF: C31H32N4O4
  • MW: 524.61000
  • Catalog: Adrenergic Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ICI 204,448 hydrochloride

ICI-204448 is a κ-opioid agonist with limited access to the CNS, ICI-204448 can displace the binding of the kappa-opioid ligand 3H-bremazocine from guinea pig cerebellum membranes[1].

  • CAS Number: 121264-04-8
  • MF: C23H27Cl3N2O4
  • MW: 501.83
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: 638.9ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 340.2ºC

Urapidil-d4 hydrochloride

Urapidil-d4 hydrochloride is the deuterium labeled Urapidil hydrochloride. Urapidil hydrochloride is an α1-adrenoceptor antagonist and 5-HT1A receptor agonist[1][2].

  • CAS Number: 1794979-63-7
  • MF: C20H26D4ClN5O3
  • MW: 427.96
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Avosentan

Avosentan(Ro 67-0565; SPP-301) is a potent, selective endothelin receptor(ETA receptor) antagonist.IC50 value:Target: ETA receptor

  • CAS Number: 290815-26-8
  • MF: C23H21N5O5S
  • MW: 479.508
  • Catalog: Endothelin Receptor
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 575.5±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 301.8±32.9 °C

PF-03654746 Tosylate

PF-03654746 Tosylate is a potent and selective histamine H3 receptor antagonist with high brain penetration. PF-03654746 Tosylate reduces allergen-induced nasal symptoms[1]. PF-03654746 Tosylate has potential for treatment of human cognitive disorders, improves cognitive efficacy and disease-modifying effects in Alzheimer's disease (AD)[2].

  • CAS Number: 1039399-17-1
  • MF: C25H32F2N2O4S
  • MW: 494.59400
  • Catalog: Histamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Neuropeptide Y (2-36) (porcine)

Neuropeptide Y (2-36) (porcine) is a neuropeptide Y5 receptor (NPY5R) agonist in rats with EC50 values of 1.2, 1.6 and 3.4 nM for receptor of Y5, Y2 and Y1 respectively. Neuropeptide Y (2-36) (porcine) can be used in studies related to obesity and eating disorders.

  • CAS Number: 102961-52-4
  • MF:
  • MW:
  • Catalog: Neuropeptide Y Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ancarolol

Ancarolol is a beta-adrenergic blocking agent.

  • CAS Number: 75748-50-4
  • MF: C18H24N2O4
  • MW: 332.39400
  • Catalog: Adrenergic Receptor
  • Density: 1.183g/cm3
  • Boiling Point: 433.7ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 216.1ºC

Clencyclohexerol

Clencyclohexerol is a β-agonist. Clencyclohexerol can be used as a growth promoter in animals[1].

  • CAS Number: 157877-79-7
  • MF: C14H20Cl2N2O2
  • MW: 319.227
  • Catalog: Adrenergic Receptor
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 514.6±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 265.0±30.1 °C

Cinalukast

Ro 24-5913 (Cinalukast) is an orally active and potent LTD4 antagonist with an IC50 value of 6.4 nM. Ro 24-5913 can be used for the research of asthma[1].

  • CAS Number: 128312-51-6
  • MF: C23H28N2O3S
  • MW: 412.54500
  • Catalog: Leukotriene Receptor
  • Density: 1.258g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bupropion D9

Bupropion D9 is a deuterium labeled Bupropion. Bupropion is an atypical antidepressant of the aminoketone group and inhibits dopamine, norepinephrine reuptake and blocks several nicotinic receptors[1].

  • CAS Number: 150988-80-0
  • MF: C13H9D9ClNO
  • MW: 248.79700
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Histamine phosphate

Histamine diphosphate is a potent agonist of histamine receptors and vasodilator. It can activate nitric oxide synthetase.

  • CAS Number: 51-74-1
  • MF: C5H15N3O8P2
  • MW: 307.14
  • Catalog: Histamine Receptor
  • Density: N/A
  • Boiling Point: 887.3ºC at 760 mmHg
  • Melting Point: 128-132 °C
  • Flash Point: 490.4ºC

MRS 1754

MRS 1754 is a selective antagonist radioligand for A2B adenosine receptor with very low affinity for A1 and A3 receptors of both humans and rats[1].

  • CAS Number: 264622-58-4
  • MF: C26H26N6O4
  • MW: 486.52200
  • Catalog: Adenosine Receptor
  • Density: 1.38g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

2-CL-IB-MECA

Namodenoson (CF-102) is a selective A3 adenosine receptor agonist (Ki = 0.33 nM). Displays 2500- and 1400-fold selectivity over A1 and A2A receptors respectively.

  • CAS Number: 163042-96-4
  • MF: C18H18ClIN6O4
  • MW: 544.731
  • Catalog: Adenosine Receptor
  • Density: 2.0±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: 209 °C
  • Flash Point: N/A

5-HT7 receptor ligand 1

5-HT7 receptor ligand 1 (Compound 5c) is a 5-HT7 receptor ligand with a Ki of 8 nM. 5-HT7 receptor ligand 1 is not hepatotoxic and exhibit moderate potential interaction with other drugs metabolized by CYP3A4 or CYP2D6[1].

  • CAS Number: 2758571-64-9
  • MF: C21H23N7
  • MW: 373.45
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

KRAS G12C inhibitor 28

KRAS G12C inhibitor 28 is a KRAS G12C inhibitor with an IC50 of 57 nM. KRAS G12C inhibitor 28 has antitumor effects (WO2021113595A1; Example 1)[1].

  • CAS Number: 2649004-88-4
  • MF: C33H36F2N5O4P
  • MW: 635.64
  • Catalog: Ras
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Fenspiride

Fenspiride, an orally active non-steroidal antiinflammatory agent, is an antagonist of H1-histamine receptor. Fenspiride inhibites phosphodiesterase 3 (PDE3), phosphodiesterase 4 (PDE4) and phosphodiesterase 5 (PDE5) activities with -log IC50 values of 3.44, 4.16 and approximately 3.8, respectively. Fenspiride can be used for the research of respiratory diseases[1][2][3].

  • CAS Number: 5053-06-5
  • MF: C15H20N2O2
  • MW: 260.332
  • Catalog: Histamine Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 408.3±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 200.7±31.5 °C

PF-04634817 succinate

PF-04634817 is a potent, orally bioavailble CCR2 and CCR5 chemokine receptor antagonist, for the treatment of diabetic nephropathies and diabetic macular oedema. Other Indication Phase 2 Discontinued

  • CAS Number: 2140301-98-8
  • MF: C25H36F3N5O3·C4H6O4
  • MW: 629.67
  • Catalog: CCR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Zelminemab

Zelminemab (AMG-301) is a human monoclonal antibody that inhibits PACAP type I (PAC1) receptor[1].

  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PF 04479745

PF-4479745 is a potent and selective 5-HT2C receptor agonist (EC50: 10 nM, ki: 15 nM). PF-4479745 can be used in the research of cardiovascular disease like hypertension[1].

  • CAS Number: 1065110-43-1
  • MF: C17H22N4
  • MW: 282.383
  • Catalog: 5-HT Receptor
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 473.4±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 240.1±28.7 °C

Topiramate

Topiramate is an anticonvulsant that antagonizes GluR5 receptors and acts as a positive allosteric modulator of GABA receptor-mediated currents.Target: GluR5 receptor; GABA receptorTopiramate (Topamax) is a structurally novel broad-spectrum antiepileptic drug (AED) with established efficacy as monotherapy or adjunctive therapy in the treatment of adult and paediatric patients with generalised tonic-clonic seizures, partial seizures with or without generalised seizures, and seizures associated with Lennox-Gastaut syndrome [1]. topiramate has been believed to be a type of antiepileptic drug that blocks spread of seizures. Thus far, the mechanisms of its actions have been proven to include use-dependent inhibition of voltage-dependent Na+ channels in neurons, potentiation of GABA (gamma-amino-butyric acid)-induced Cl- influx, and inhibitory effects on inward currents by antagonizing kainate/alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors [2].Topiramate (median average dosage 5.1 mg/kg/day) was also found to be useful as adjunctive therapy in the management of Lennox-Gastaut syndrome and significantly reduced the mean frequency of drop attacks by 14.8% compared with an increase of 5.1% with placebo. Further gains in seizure control were made in a nonblind extension of this trial where the mean topiramate dosage was 10 mg/kg/day. Nine of 11 patients in 1 pilot trial of children with otherwise intractable West syndrome, and 5 of 10 in another, achieved a > or =50% reduction in seizure rate with topiramate (target dosage up to 24 mg/kg/day) [3].Clinical indications: Epilepsy; Lennox Gastaut syndrome; Migraine; Seizure disorder Toxicity:abdominal pain; agitation; blurred vision; convulsions; depression; dizziness; double vision; drowsiness; impaired coordination; impaired mental activity; low blood pressure; reduced consciousness; severe diarrhea; sluggishness and speech problems.

  • CAS Number: 97240-79-4
  • MF: C12H21NO8S
  • MW: 339.362
  • Catalog: mGluR
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 438.7±55.0 °C at 760 mmHg
  • Melting Point: 125ºC
  • Flash Point: 219.1±31.5 °C

Alcaftadine

Alcaftadine(R89674) is a H1 histamine receptor antagonist, which is used to prevent eye irritation brought on by allergic conjunctivitis.Target: H1 Histamine ReceptorAlcaftadine is a broad-spectrum antihistamine displaying a high affinity for histamine H1 and H2 receptors and a lower affinity for H4 receptors. alcaftadine was more effective than placebo and at least as effective as olopatadine 0.01% in preventing ocular itching at 15 minutes and at 16 hours after administration. Alcaftadine 0.025% ophthalmic solution has been approved by the U.S. Food and Drug Administration for prevention of itching associated with allergic conjunctivitis in patients over 2 years of age [1]. Alcaftadine is a safe and effective option for the prevention of ocular itching associated with allergic conjunctivitis, is dosed once daily, and is competitively priced among prescription medications for allergic conjunctivitis [2].

  • CAS Number: 147084-10-4
  • MF: C19H21N3O
  • MW: 307.389
  • Catalog: Histamine Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 556.2±60.0 °C at 760 mmHg
  • Melting Point: 167 °C
  • Flash Point: 290.2±32.9 °C

Rasarfin

Rasarfin is a dual Ras and ARF6 inhibitor[1].

  • CAS Number: 674359-73-0
  • MF: C23H24ClN3O3
  • MW: 425.91
  • Catalog: Ras
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Neuropeptide Y (18-36) trifluoroacetate salt

Neuropeptide Y (18-36) (porcine) is a competitive neuropeptide Y (NPY) cardiac receptor antagonist. Neuropeptide Y (18-36) (porcine) inhibits the binding of I-NPY to rat cardiac ventricular membranes in a concentration-dependent manner with an IC50 value of 158 nM and an Ki value of 140 nM. Neuropeptide Y (18-36) (porcine) can be used for the research of congestive heart failure[1].

  • CAS Number: 114495-97-5
  • MF: C112H174N36O27
  • MW: 2456.80000
  • Catalog: Neuropeptide Y Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CCR1 inhibitor 19e

CCR1 inhibitor 19e is a novel potent, selective CCR1 antagonist with IC50 of 6.8 nM, inhibits CCR1chemotaxis in THP-1 cells with IC50 of 28 nM.

  • CAS Number: 1220026-26-5
  • MF: C20H16FN5O3S
  • MW: 425.438
  • Catalog: CCR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

[D-Trp34]-Neuropeptide Y

[D-Trp34]-Neuropeptide Y is a potent and selective neuropeptide Y (NPY) Y5 receptor agonist. [D-Trp34]-Neuropeptide Y is a significantly less potent agonist at the NPY Y1, Y2, Y4, and y6 receptors. [D-Trp34]-Neuropeptide Y markedly increases food intake in rats[1][2].

  • CAS Number: 153549-84-9
  • MF: C196H289N55O56
  • MW: 4311.77
  • Catalog: Neuropeptide Y Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

1-Benzoyl-2-[[trans-4-[[[[2-nitro-4-(trifluoromethyl)phenyl]sulfonyl]amino]methyl]cyclohexyl]carbonyl]hydrazine

S 25585 is a potent and selective neuropeptide Y (NPY) Y5 receptor antagonist. S 25585 reduces food intake but not through blockade of the NPY Y5 receptor[1].

  • CAS Number: 263849-50-9
  • MF: C22H23F3N4O6S
  • MW: 528.501
  • Catalog: Neuropeptide Y Receptor
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TH-Z835

TH-Z835 is a mutant selective KRAS (G12D) inhibitor with an IC50 of 1.6 μM. TH-Z835 inhibits both mantGMPPNP/GPPNP exchange and GPPNP/mantGMPPNP exchange[1].

  • CAS Number: 2766209-50-9
  • MF: C30H38N6O
  • MW: 498.66
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A