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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Dynorphin A trifluoroacetate salt

Dynorphin A, an endogenous opioid peptide, is a highy potent kappa opioid receptor (KOR) activator. Dynorphin A also serve as an agonist for other opioid receptors,  such as mu (MOR) and delta (DOR)[1].

  • CAS Number: 80448-90-4
  • MF: C99H155N31O23
  • MW: 2147.484
  • Catalog: Opioid Receptor
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Clobenpropit dihydrobromide

Clobenpropit dihydrobromide is a potent histamine H3R antagonist/inverse agonist with a pEC50 of 8.07 for histamine H3LR[1]. Clobenpropit dihydrobromide acts as partial agonist at histamine H4 receptors (Ki 13 nM). Clobenpropit dihydrobromide also binds to serotonin 5-HT3 receptors (Ki 7.4 nM) and α2A/α2C adrenoceptors (Ki 17.4/7.8 nM)[2]. Clobenpropit dihydrobromide increases apoptosis[3].

  • CAS Number: 145231-35-2
  • MF: C14H19Br2ClN4S
  • MW: 470.654
  • Catalog: Histamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 205 °C
  • Flash Point: N/A

RPT193

RPT193 is an orally active inhibitor of CCR4, blocks the recruitment of Th2 inflammatory immune cells into inflamed tissues. RPT193 can be used for allergic inflammation in atopic dermatitis, asthma, and other diseases research[1].

  • CAS Number: 2366152-15-8
  • MF: C27H34Cl3N5O2
  • MW: 566.95
  • Catalog: CCR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EP4 receptor antagonist 4

EP4 receptor antagonist 4 is an EP4 receptor agonist with the human pEC50 value of 6.3[1].

  • CAS Number: 691869-12-2
  • MF: C19H14N2OS
  • MW: 318.39
  • Catalog: Prostaglandin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Lafutidine-d10

Lafutidine-d10 is deuterium labeled Lafutidine. Lafutidine (FRG-8813) is a histamine H2-receptor antagonist (H2RA), with proven gastric mucosal protective effects. Lafutidine can be used for the research of gastroesophageal reflux disease[1].

  • CAS Number: 1795136-26-3
  • MF: C22H19D10N3O4S
  • MW: 441.61
  • Catalog: Histamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

H4R antagonist 2

H4R antagonist 2 (page 68), a Furo[3,2-d]pyrimidine derivative, is a potent H4R antagonist. H4R antagonist 2 can be used in research of rheumatoid arthritis[1].

  • CAS Number: 1148115-99-4
  • MF: C13H17N5O
  • MW: 259.31
  • Catalog: Histamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Opiranserin hydrochloride

Opiranserin (VVZ-149) hydrochloride, a non-opioid and non-NSAID analgesic candidate, is a dual antagonist of glycine transporter type 2 (GlyT2) and serotonin receptor 2A (5HT2A), with IC50s of 0.86 and 1.3 μM, respectively. Opiranserin hydrochloride shows antagonistic activity on rP2X3 (IC50=0.87 μM). Opiranserin hydrochloride is development as an injectable agent for the treatment of postoperative pain[1][2][3].

  • CAS Number: 1440796-75-7
  • MF: C21H35ClN2O5
  • MW: 430.97
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GPR40/FFAR1 modulator 1

GPR40/FFAR1 modulator 1 is an agonist and an allosteric modulator for Gq-coupled free fatty acid receptor 1 (GPR40/FFAR1)[1].

  • CAS Number: 874755-26-7
  • MF: C21H19N5O3
  • MW: 389.41
  • Catalog: GPR40
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

A-192621

A-192621 is a potent, nonpeptide, orally active and selective endothelin B (ETB) receptor antagonist with an IC50 of 4.5 nM and a Ki of 8.8 nM. The selectivity of A-192621 is 636-fold higher than ETA (IC50 of 4280 nM and Ki of 5600 nM). A-192621 promotes apoptosis in PASMCs. A-192621 alos causes elevation of arterial blood pressure and an elevation in the plasma ET-1 level[1][2][3].

  • CAS Number: 195529-54-5
  • MF: C33H38N2O6
  • MW: 558.66500
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CYN 154806

CYN 154806, a cyclic octapeptide, is a potent and selective somatostatin sst2 receptor antagonist, with pIC50 values of 8.58, 5.41, 6.07, 5.76 and 6.48 for human recombinant sst2, sst1, sst3, sst4 and sst5 receptors respectively[1][2].

  • CAS Number: 183658-72-2
  • MF: C56H68N12O14S2
  • MW: 1197.34
  • Catalog: Somatostatin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ADX71743

ADX71743 is a highly selective, noncompetitive and brain-penetrant metabotropic glutamate receptor 7 negative allosteric modulator (mGlu7 NAM). ADX71743 has anxiolytic-like activity[1][2].

  • CAS Number: 1431641-29-0
  • MF: C17H19NO2
  • MW: 269.34
  • Catalog: mGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TUG-905

TUG-905 is a potent GPR40 agonist with an pEC50 value of 7.03. TUG-905 increases hypothalamic cell proliferation and survival. TUG-905 reduces body mass and increases the POMC mRNA expression[1][2].

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

A2A receptor antagonist 1

A2A receptor antagonist 1 is an antagonist of both adenosine A2A receptor and A1 receptor with Kis of 4 and 264 nM, respectively.

  • CAS Number: 443103-97-7
  • MF: C16H12FN5O
  • MW: 309.3
  • Catalog: Adenosine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Hydroxyzine dihydrochloride

Hydroxyzine Dihydrochloride is a histamine H1-receptor antagonist.Target: Histamine H1-ReceptorHydroxyzine inhibits carbachol (10 μM)-induced serotonin release by 34% at 10 μM, by 25% 1 μM and by 17% 0.1 μM in pretreated bladder slices for 60 min [1]. Hydroxyzine (0.1 mM) treatment inhibits the progression and severity of EAE by 50% and the extent of mast cell degranulation by 70% in Lewis rats with allergic encephalomyelitis (EAE) [2]. Hydroxyzine (500 M) significantly increases transport of etoposide to the serosal site in the jejunal everted sacs. Hydroxyzine significantly reduces the efflux and approximately 2.4 g/mL of etoposide in the jejunum and ileum. Hydroxyzine (0.2 μg/mL) significantly enhances the efflux of RH123 to the lumen [3].Hydroxyzine (500 μM) significantly decreases the steady-state etoposide concentration 2-fold, where the steady-state concentration reached about 0.055 μM/mL in Sprague-Dawley rats [3]. Hydroxyzine (12.5 mg/kg, 25 mg/kg and 50 mg/kg i.p.) shows little direct analgesic activity but markedly potentiates only the effect of morphine on the vocalization after-discharge which represents the affective component of pain in rats. Hydroxyzine (50 mg/kg i.p.) potentiates morphine on the tail-flick test, while Hydroxyzine (12.5 mg/kg i.p.) decreases morphine antinociception in rats [4].

  • CAS Number: 2192-20-3
  • MF: C21H29Cl3N2O2
  • MW: 447.826
  • Catalog: Histamine Receptor
  • Density: 1.182 g/cm3
  • Boiling Point: 499.2ºC at 760 mmHg
  • Melting Point: 190-192°C
  • Flash Point: 255.7ºC

Flunarizine

Flunarizine is a potent dual Na+/Ca2+ channel (T-type) blocker. Flunarizine is a D2 dopamine receptor antagonist. Flunarizine shows anticonvulsive and antimigraine activity, and peripheral vasodilator effects[1][2][3][4][5].

  • CAS Number: 52468-60-7
  • MF: C26H26F2N2
  • MW: 404.49500
  • Catalog: Dopamine Receptor
  • Density: 1.17 g/cm3
  • Boiling Point: 511.3ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: N/A

Alniditan

Alniditan is a potent 5-HT1B/1D receptors agonist, with IC50 of 1.7 and 1.3 nM in HEK 293 cells, and pKi value of 8.96 and 9.40 for 5-HT1B/1D receptors, respectively.

  • CAS Number: 152317-89-0
  • MF: C17H26N4O
  • MW: 302.41500
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MK 0893

MK 0893 is a potent, selective glucagon receptor antagonist with IC50 of 6.6 nM, and > 200 fold selectivity against GIPR, PAC1, GLP-1R, VPAC1 and VPAC2.

  • CAS Number: 870823-12-4
  • MF: C32H27Cl2N3O4
  • MW: 588.481
  • Catalog: Glucagon Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 814.0±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 446.1±34.3 °C

Bunitrolol

Bunitrolol is a beta-adrenergic antagonist. Bunitrolol has intrinsic sympathomimetic activity. Bunitrolol can be used for the research of ischemic myocardium[1].

  • CAS Number: 34915-68-9
  • MF: C14H20N2O2
  • MW: 248.32
  • Catalog: Adrenergic Receptor
  • Density: 1.09g/cm3
  • Boiling Point: 414.2ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 204.3ºC

ZT 52656A hydrochloride

ZT 52656A is a selective kappa opioid agonist, used for the prevention or alleviation of pain in the eye.

  • CAS Number: 115730-24-0
  • MF: C19H26ClF3N2O
  • MW: 390.87
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Dobutamine tartrate

Dobutamine tartrate is a synthetic catecholamine that acts on α1-AR, β1-AR, β2-AR (α-1, β-1 andβ-2 adrenoceptors). Dobutamine tartrate is a selective β1-AR agonist, relatively weak activity at α1-AR and β2-AR. Dobutamine tartrate can increase cardiac output and correct hypoperfusion[1][2][3][4].

  • CAS Number: 101626-66-8
  • MF: C22H29NO9
  • MW: 451.47
  • Catalog: Adrenergic Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bremelanotide Acetate

Bremelanotide Acetate is a melanocortin agonist.IC50 value:Target: melanocortinin vivo: Bremelanotide is a novel drug candidate for the treatment of male and female sexual dysfunction. Bremelanotide has shown promise in effectively treating erectile dysfunction (ED) without the cardiovascular effects found in ED drugs currently available. Bremelanotide works through a mechanism of action involving the central nervous system rather than directly on the vascular system. As a result, it may offer significant safety and efficacy benefits over currently available products.

  • CAS Number: 1607799-13-2
  • MF: C52H72N14O12
  • MW: 1085.215
  • Catalog: Endocrinology
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Elinzanetant

Elinzanetant is a neurokinin receptors antagonist used for the research of Schizophrenia[1].

  • CAS Number: 929046-33-3
  • MF: C33H35F7N4O3
  • MW: 668.64
  • Catalog: Neurokinin Receptor
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 672.1±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 360.3±31.5 °C

MF498

MF498 is a novel and selective E prostanoid receptor 4 (EP4 receptor) antagonist, displayed strong binding affinity for the EP4 receptor with Ki of 0.7 nM.Ki value: 0.7 nMTarget: EP4 receptorin vitro: MF498 also displays a relatively good selectivity over other prostanoid receptors, does not compromise the mucosal integrity in the gastrointestinal tract.MF498 inhibits PGE2-stimulated cAMP accumulation in a dose-dependent manner with IC50 values of 1.7 and 17 nM in the absence and presence of 10% serum, respectively. in vivo: MF498 relieves joint inflammation and pain in rodent models of rheumatoid and osteoarthritis. MF498 on inflammation in adjuvant-induced arthritis (AIA), a rat model for rheumatoid arthritis (RA), and joint pain in a guinea pig model of iodoacetate-induced osteoarthritis (OA).

  • CAS Number: 915191-42-3
  • MF: C32H33N3O7S
  • MW: 603.685
  • Catalog: Prostaglandin Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MDA-19

MDA 19 is a selective human CB2 receptor agonist with Ki of 43.3 nM. IC50 Value: 43.3 nM(Ki)Target: CB2 receptorin vitro: MDA19 displayed 4-fold-higher affinity at the human CB(2) than at the human CB1 receptor (K(i) = 43.3 +/- 10.3 vs 162.4 +/- 7.6 nM) and nearly 70-fold-higher affinity at the rat CB2 than at the rat CB1 receptor (K(i) = 16.3 +/- 2.1 vs 1130 +/- 574 nM). In guanosine triphosphate (GTP)gamma[(35)S] functional assays, MDA19 behaved as an agonist at the human CB1 and CB2 receptors and at the rat CB1 receptor but as an inverse agonist at the rat CB2 receptor. In 3',5'-cyclic adenosine monophosphate (cAMP) assays, MDA19 behaved as an agonist at the rat CB1 receptor and exhibited no functional activity at the rat CB(2) receptor. In extracellular signal-regulated kinases 1 and 2 activation assays, in vivo: MDA19 behaved as an agonist at the rat CB2 receptor. MDA19 attenuated tactile allodynia produced by spinal nerve ligation or paclitaxel in a dose-related manner in rats and CB2(+/+) mice but not in CB2(-/-) mice, indicating that CB2 receptors mediated the effects of MDA19. MDA19 did not affect rat locomotor activity.

  • CAS Number: 1048973-47-2
  • MF: C21H23N3O2
  • MW: 349.426
  • Catalog: Cannabinoid Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

β2AR agonist /M-receptor antagonist-1

β2AR agonist /M-receptor antagonist-1 is a potent dual muscarinic antagonist/beta 2 agonist (MABA). β2AR agonist /M-receptor antagonist-1 potently relaxes either Carbachol (HY-B1208)-induced contraction, in the absence (MABA) or presence of Propranolol (M3; HY-B1208), or Histamine (HY-B1204)-induced contraction (β2)[1][2].

  • CAS Number: 2772700-36-2
  • MF: C33H40FN5O5S2
  • MW: 669.83
  • Catalog: Adrenergic Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Met-Enkephalin acetate salt

Tyr-Gly-Gly-Phe-Met-OH regulates human immune function and inhibits tumor growth via binding to the opioid receptor.

  • CAS Number: 58569-55-4
  • MF: C27H35N5O7S
  • MW: 573.66100
  • Catalog: Peptides
  • Density: 1.324 g/cm3
  • Boiling Point: 1052.9ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 590.6ºC

Salvinorin B Mesylate

Mesyl Salvinorin B is a potent and selective kappa opioid receptor (KOP-r) agonist. Mesyl Salvinorin B prevents the ADE (Alcohol deprivation effect) in mice. Mesyl Salvinorin B dose-dependently reduces alcohol intake and preference in CED (chronic escalation drinking) mice[1][2].

  • CAS Number: 862073-79-8
  • MF: C22H28O9S
  • MW: 468.52
  • Catalog: Opioid Receptor
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 649.4±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 346.6±31.5 °C

AM630

6-Iodopravadoline (AM630) is a selective CB2 antagonist with Ki of 31.2 nM, and displays 165-fold selectivity over CB1 receptors.

  • CAS Number: 164178-33-0
  • MF: C23H25IN2O3
  • MW: 504.361
  • Catalog: Cannabinoid Receptor
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 605.9±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 320.3±31.5 °C

ATL-801

ATL-801, an A2B receptor selective antagonist, ameliorates murine colitis[1].

  • CAS Number: 1000005-71-9
  • MF: C24H25N7O3
  • MW: 459.50000
  • Catalog: Adenosine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MRS 2578

MRS2578 is a potent P2Y6 receptor antagonist with IC50 of 37 nM, exhibits insignificant activity at P2Y1, P2Y2, P2Y4,and P2Y11 receptors.IC50 value: 37 nM [1]Target: P2Y6 receptorin vitro: MRS2578 selectively blocks P2Y6 receptor activity versus activity at P2Y1, P2Y2, P2Y4 or P2Y11 receptors. MRS2578 (1 μM) completely blocks the protection by UDP undergoing TNFalpha-induced apoptosis in 1321N1 astrocytoma cells [1]. MRS 2578 inhibits basal NF-κB activity in time and dose dependent manner in HMEC-1 cells transfected with 0.25 μg NF-κB promoter reporter. MRS 2578 (10 μM) completely abolishes TNF-α induced NF-κB reporter activity in HMEC-1 cells. MRS 2578 (10 μM) significant reduces TNF-α–induced proinflammatory gene expression in HMEC-1 cells [2]. MRS2578-treated mice shows reduced bronchial hyperresponsiveness toward methacholine in OVA-sensitized mice. MRS2578 completely blocks UDP-induced the release of IL-6, KC, and IL-8 in lung epithelial cells [3]. in vivo: MRS 2578 (10 μM) attenuates Keratinocyte-derived chemokine serum protein levels in LPS-induced vascular inflammation in C57BL/6 mice [2]. MRS2578 (10 μM, intratracheally) reduces BALF eosinophilia and the levels of IL-5 and IL-13 in the BALF in OVA-sensitized mice and leads to a markedly attenuated change in methacholine responsiveness after OVA challenge. MRS2578 (10 μM, intratracheally) inhibits house dust mite–induced allergic airway inflammation in OVA-sensitized mice. MRS2578 (10 μM, intratracheally) reduces of IL-6 and KC levels in BALF in OVA-sensitized mice [4].

  • CAS Number: 711019-86-2
  • MF: C20H20N6S4
  • MW: 472.673
  • Catalog: P2Y Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 652.7±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 348.5±34.3 °C