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.


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Sarizotan

Sarizotan (EMD 128130) is an orally active serotonin 5-HT1A receptor and dopamine receptor agonist. Sarizotan (EMD 128130) exhibits IC50 values of 6.5 nM (rat 5-HT1A), 0.1 nM (human 5-HT1A), 15.1 nM (rat D2), 17 nM (human D2), 6.8 nM (human D3) and 2.4 nM (human D4.2), respectively[1].

  • CAS Number: 351862-32-3
  • MF: C22H21FN2O
  • MW: 350.42900
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

1H-Tetrazole-5-carboxamide, N-(5-(3-(4-acetyl-3-hydroxy-2-propylphenox y)propoxy)-4-chloro-2-methylphenyl)-, monosodium salt

CGP-35949 sodium is a LTD4 antagonist with phospholipase inhibitory activity. CGP-35949 sodium can be used for research of asthma[1].

  • CAS Number: 111130-13-3
  • MF: C23H25ClN5NaO5
  • MW: 509.92
  • Catalog: Leukotriene Receptor
  • Density: N/A
  • Boiling Point: 597.3ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 315ºC

ML 184

ML-184 (ML184) is a potent, selective GPR55 agonist with EC50 of 263 nM, >120-fold, 83-fold, and 57-fold selectivity against GPR35, CB1 and CB2; shows activity in activating the downstream responses of ERK phosphorylation and PKC β II translocation.

  • CAS Number: 794572-10-4
  • MF: C25H34N4O3S
  • MW: 470.628
  • Catalog: GPR55
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 681.4±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 365.9±34.3 °C

JD-5037

JD-5037 is a novel, peripherally restricted CB1R antagonist with an IC50 of 1.5 nM.

  • CAS Number: 1392116-14-1
  • MF: C27H27Cl2N5O3S
  • MW: 572.506
  • Catalog: Cannabinoid Receptor
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 731.3±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 396.1±35.7 °C

Atrasentan

Atrasentan is an endothelin receptor antagonist with IC50 of 0.0551 nM for ETA.

  • CAS Number: 173937-91-2
  • MF: C29H38N2O6
  • MW: 510.62200
  • Catalog: Endothelin Receptor
  • Density: 1.188g/cm3
  • Boiling Point: 659.4ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 352.6ºC

S 18886

Terutroban is a thromboxane-prostaglandin receptor antagonist.

  • CAS Number: 165538-40-9
  • MF: C20H22ClNO4S
  • MW: 407.91100
  • Catalog: Prostaglandin Receptor
  • Density: 1.389g/cm3
  • Boiling Point: 591.818ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 311.721ºC

ADX-88178

ADX88178 is a potent positive allosteric modulator for metabotropic glutamate receptor 4 (mGluR4) with EC50 of 4 nM for human mGluR4.

  • CAS Number: 1235318-89-4
  • MF: C12H12N6S
  • MW: 272.32900
  • Catalog: mGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CHF-6366

CHF-6366 is a potent M3 muscarinic antagonist and β2-adrenergic receptors agonist with pKi values of 10.4 and 11.4, respectively. CHF-6366 is also a weak calcium channel inhibitor (IC50~50 μM). CHF-6366 inhibits bronchoconstriction in guinea pigs. CHF-6366 can be used to research chronic obstructive pulmonary disease (COPD)[1].

  • CAS Number: 1615208-41-7
  • MF: C42H48N6O8
  • MW: 764.87
  • Catalog: Adrenergic Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Velusetrag hydrochloride

Velusetrag (TD-5108) is a potent, selective and oral 5-HT4 receptor agonist with pKi of 7.7, shows >500-fold selectivity over other 5-HT receptors; displays >25-fold selectivity over other biogenic amine receptors, and no effect on hERG channels; increases the contractility of the canine antrum, duodenum and jejunum with higher potency than tegaserod, demonstrates robust in vivo activity in the guinea pig, rat and dog gastrointestinal tracts. Other Indication Phase 2 Clinical

  • CAS Number: 866933-51-9
  • MF: C25H37ClN4O5S
  • MW: 541.103
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TRIPELENNAMINE CITRATE

Tripelennamine citrate, an ethylenediamine derivative, is a potent histamine H1-receptor antagonist. Tripelennamine citrate lessens the allergic response of the organism caused by histamine. Tripelennamine citrate can be used for the research of rhinitis, conjunctivitis, and allergic and anaphylactic reactions[1][2][3].

  • CAS Number: 6138-56-3
  • MF: C22H29N3O7
  • MW: 447.48200
  • Catalog: Histamine Receptor
  • Density: N/A
  • Boiling Point: 387.8ºC at 760 mmHg
  • Melting Point: 106-110°
  • Flash Point: 188.3ºC

Epifriedelal acetate

Epifriedelanol acetate (Compound Ⅲc) is a nature product. Epifriedelanol acetate can be isolated from Pachysandra terminalis Sieb[1].

  • CAS Number: 2259-07-6
  • MF: C32H54O2
  • MW: 470.770
  • Catalog: Cannabinoid Receptor
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 461.9±13.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 264.4±7.4 °C

K777

K777 is a potent, orally active and irreversible cysteine protease inhibitor. K777 is also a potent CYP3A4 inhibitor with an IC50 of 60 nM and a selective CCR4 antagonist featuring the potent chemotaxis inhibition. K777 irreversibly inhibits Cruzain, the major cysteine protease of Trypansoma cruzi, and cathepsins B and L. K777 is a broad-spectrum antiviral by targeting cathepsin-mediated cell entry. K777 inhibits SARS-CoV and EBOV pseudovirus entry with IC50 values of 0.68 nM and 0.87 nM, respectively[1][2][3].

  • CAS Number: 233277-99-1
  • MF: C32H38N4O4S
  • MW: 574.73
  • Catalog: CCR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Xanthurenic acid-d4

Xanthurenic acid-d4 is the deuterium labeled Xanthurenic acid[1]. Xanthurenic acid is a putative endogenous Group II metabotropic glutamate receptor agonist, on sensory transmission in the thalamus[2].

  • CAS Number: 1329611-28-0
  • MF: C10H3D4NO4
  • MW: 209.191
  • Catalog: Apoptosis
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 514.4±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 264.9±30.1 °C

2-Arachidonoylglycerol-d11

2-Arachidonoylglycerol-d11 is deuterium labeled 2-Arachidonoylglycerol.2-Arachidonoylglycerol is a second endogenous cannabinoid ligand in the central nervous system[1].

  • CAS Number: 2260670-54-8
  • MF: C23H27D11O4
  • MW: 389.61
  • Catalog: Cannabinoid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

angiotensin iv

Angiotensin II (3-8), human is a less effective agonist at the angiotensin AT1 receptor.

  • CAS Number: 12676-15-2
  • MF: C40H54N8O8
  • MW: 774.90600
  • Catalog: Peptides
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ML-109

ML-109 is a potent and full thyroid stimulating hormone receptor (TSHR) agonist, with an EC50 of 40 nM.

  • CAS Number: 1186649-91-1
  • MF: C31H29N3O5
  • MW: 523.58
  • Catalog: TSH Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Iloprost-d4

Iloprost-d4 (Ciloprost-d4) is the deuterium labeled Iloprost. Iloprost (ZK 36374) is a synthetic analogue of prostacyclin PGI2[1][2].

  • CAS Number: 1035094-10-0
  • MF: C22H28D4O4
  • MW:
  • Catalog: Prostaglandin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Naloxonazine dihydrochloride

Naloxonazine dihydrochloride is a specific μ-opioid receptor antagonist with an IC50 of 5.4 nM. Naloxonazine dihydrochloride also shows anti-leishmanial activity[1][2][3].

  • CAS Number: 880759-65-9
  • MF: C38H43ClN4O6
  • MW: 687.22400
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SB-423562

SB-423562 is a short-acting calcium-sensing receptor (CaR) antagonist.

  • CAS Number: 351490-27-2
  • MF: C26H32N2O4
  • MW: 436.54300
  • Catalog: CaSR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Nocloprost

Nocloprost, a prostaglandin E2 (PGE2) analog, is an orally active EP1- and EP3-receptor agonist. Nocloprost inhibits evoked [3H]ACh release. Nocloprost has gastroprotective and ulcer-healing properties. Nocloprost accelerates the healing of chronic gastric ulcerations and enhances mucosal growth in rats[1][2].

  • CAS Number: 79360-43-3
  • MF: C22H37ClO4
  • MW: 400.98000
  • Catalog: Prostaglandin Receptor
  • Density: 1.1g/cm3
  • Boiling Point: 539.8ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 280.3ºC

[Pro9]-Substance P

[Pro9]-Substance P is a potent, reversible and selective agonist of NK-1 tachykinin receptors with an EC50 of 0.93 nM[1].

  • CAS Number: 104486-69-3
  • MF: C66H102N18O13S
  • MW: 1387.69000
  • Catalog: Neurokinin Receptor
  • Density: 1.43g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ZG1077

ZG1077 is a covalent KRAS G12C inhibitor. ZG1077 can be used in the research of non-small cell lung cancer (NSCLC)[1].

  • CAS Number: 2670380-82-0
  • MF: C33H33F2N5O5S
  • MW: 649.71
  • Catalog: Ras
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(S)-4-BENZYL-1,3-THIAZOLIDINE-2-ONE

(S)-4C3HPG ((S)-4-Carboxy-3-hydroxyphenylglycine) is an antagonist of metabotropic glutamate receptor 1a (mGluR 1a) and an agonist of GluR2. (S)-4C3HPG has the anticonvulsant activity and protects against audiogenic seizures in DBA/2 mice[1].

  • CAS Number: 85148-82-9
  • MF: C9H9NO5
  • MW: 211.17100
  • Catalog: mGluR
  • Density: 1.596g/cm3
  • Boiling Point: 479.1ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 243.6ºC

SB742457

SB742457 is a highly selective 5-HT6 receptor antagonist with pKi of 9.63; exhibits >100-fold selectivity over other receptors.IC50 Value: 9.63 (pKi)Target: 5-HT6 ReceptorSB-742457, a 5-HT6 receptor antagonist, which extends into Alzheimer disease (AD) sufferers further highlights the therapeutic promise of this mechanistic approach. Alzheimer's disease is a devastating neurological condition characterized by a progressive decline in cognitive performance accompanied by behavioral and psychological syndromes, such as depression and psychosis. With the subsequent development of selective 5-HT6 receptor antagonists, preclinical studies in rodents and primates have elucidated the function of this receptor subtype in more detail. It is increasingly clear that blockade of 5-HT6 receptors leads to an improvement of cognitive performance in a wide variety of learning and memory paradigms and also results in anxiolytic and antidepressant-like activity. SB-742457 is generally safe and well tolerated and may be efficacious in Alzheimer disease.

  • CAS Number: 607742-69-8
  • MF: C19H19N3O2S
  • MW: 353.438
  • Catalog: 5-HT Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 608.3±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 321.7±28.7 °C

1-[[2'-(2,5-Dihydro-5-oxo-1,2,4-oxadiazol-3-yl)[1,1'-biphenyl]-4-yl]methyl]-2-ethoxy-1H-benzimidazole-7-carboxylic acid methyl ester

Azilsartan methyl ester, a derivative of Azilsartan (HY-14914), is an angiotensin II receptor antagonist that plays an important role in hypertension[1].

  • CAS Number: 147403-52-9
  • MF: C26H22N4O5
  • MW: 470.477
  • Catalog: Angiotensin Receptor
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 652.0±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 348.1±34.3 °C

KRAS inhibitor-8

KRAS inhibitor-8 is a potent KRAS G12C inhibitor, extracted from patent WO2017087528A1, compound C[1].

  • CAS Number: 2022986-70-3
  • MF: C26H24ClF4N5O3
  • MW: 565.95
  • Catalog: Ras
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

L-Glutamine-1-13C

L-Glutamine-1-13C (L-Glutamic acid 5-amide-1-13C) is the 13C-labeled L-Glutamine. L-Glutamine (L-Glutamic acid 5-amide) is a non-essential amino acid present abundantly throughout the body and involved in many metabolic processes. L-Glutamine provides a source of carbons for oxidation in some cells[1][2].

  • CAS Number: 159663-16-8
  • MF: C413CH10N2O3
  • MW: 147.14
  • Catalog: Ferroptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cetirizine-d4

Cetirizine D4 is a deuterium labeled Cetirizine. Cetirizine, a second-generation antihistamine and the carboxylated metabolite of hydroxyzine, is a specific, orally active and long-acting histamine H1-receptor antagonist. Cetirizine marks antiallergic properties and inhibits eosinophil chemotaxis during the allergic response[1][2][3].

  • CAS Number: 1219803-84-5
  • MF: C21H21D4ClN2O3
  • MW: 392.91200
  • Catalog: Histamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Fingolimod

Fingolimod is a sphingosine 1-phosphate (S1P) antagonist with IC50 of 0.033 nM in K562 and NK cells.

  • CAS Number: 162359-55-9
  • MF: C19H33NO2
  • MW: 307.471
  • Catalog: LPL Receptor
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 479.5±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 243.8±28.7 °C

AMG 837 (calcium hydrate)

AMG 837 calcium hydrate is a potent GPR40 agonist(EC50=13 nM) with a superior pharmacokinetic profile and robust glucose-dependent stimulation of insulin secretion in rodents.IC50 value: 13 nM (EC50) [1]Target: GPR40 agonistAMG 837 displayed the expected two-fold increase in potency on GPR4 (EC50 = 13 [±7] nM) compared to the racemic compound and its activity crossed over to the rat and mouse forms of GPR40 (EC50 = 23 and 13 nM, respectively). AMG 837 was found to be a partial agonist on GPR40 with maximal activity 85% of that shown by DHA under our standard assay conditions. AMG 837 is a highly potent stimulator of insulin secretion in MIN6 cells with an EC50 comparable to that seen in the aequorin Ca2+-flux assay. showedno significant activity in cell-based assays against PPARα, δ, and γ. An external panel of 64 receptors also revealed no significant activity with the exception of weak inhibition (IC50 = 3 uM) on the a2-adrenergic receptor. Overall, AMG 837 was both highly potentand selective in vitro.

  • CAS Number: 1259389-38-2
  • MF: C26H22F3O4-
  • MW: 455.45
  • Catalog: GPR40
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A