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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GB-6

GB-6 is a short linear peptide that targets the gastrin releasing peptide receptor (GRPR). GRPR is overexpressed in pancreatic cancer. Based on the tumor selectivity and tumor-specific accumulation properties of GB-6, GB-6 labeled with near infrared (NIR) fluorescent dyes or radionuclide netium-99m (99mTc) can be used as a high-contrast imaging probe. GB-6 has excellent in vivo stability, with tumor to pancreatic and intestinal fluorescence signal ratios of 5.2 and 6.3, respectively, in SW199 0 subcutaneous xenograft models. GB-6 can rapidly target tumors and accurately delineate tumor boundaries, which has broad application prospects[1].

  • CAS Number: 2413262-74-3
  • MF: C32H45N11O8
  • MW: 711.77
  • Catalog: Bombesin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BMS-753426

BMS-753426 is a potent and orally bioavailable antagonist of CCR2.

  • CAS Number: 1004536-52-0
  • MF: C25H33F3N6O2
  • MW: 506.56
  • Catalog: CCR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Maceneolignan H

Maceneolignan H (Compound 8) is a neolignane compound isolated from the arils of Myristica fragrans. Maceneolignan H is a selective CCR3 antagonist (EC50 = 1.4 μM). Maceneolignan H has the potential for the research of allergic diseases[1].

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

Tocrifluor T1117

Tocrifluor 1117 (T1117), a fluorescent form of the cannabinoid CB1 receptor antagonist AM251, is a selective fluorescent GPR55 ligand. Tocrifluor 1117 is a potent tool for identifying the cellular location of cannabinoid receptors (including GPR55 in living tissues) (Ex/Em=543/590 nm)[1][2].

  • CAS Number: 1186195-59-4
  • MF: C56H53Cl2N7O5
  • MW: 974.970
  • Catalog: Cannabinoid Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CAY10471 Racemate

CAY10471 Racemate (TM30089 Racemate) is a potent and highly selective prostaglandin D2 receptor CRTH2 antagonist, with a Ki of 0.6 nM for hCRTH2, selective over human thromboxane A2 receptor TP (Ki, >10000 nM) or PGD2 receptor DP (Ki, 1200 nM). CAY10471 Racemate also has effect on mouse and rat orthologs of CRTH2[1].

  • CAS Number: 844639-57-2
  • MF: C21H21FN2O4S
  • MW: 416.46600
  • Catalog: Prostaglandin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SRX246

SRX246 is a potent, CNS-penetrant, highly selective, orally bioavailable vasopressin 1a (V1a) receptor antagonist (Ki=0.3 nM for human V1a). SRX246 has no interaction at V1b and V2 receptors. SRX246 also displays negligible binding at 64 others receptors classes, including 35 G-proteincoupled receptors. SRX246 is under development for the treatment of stress-related disorders[1].

  • CAS Number: 512784-93-9
  • MF: C42H49N5O5
  • MW: 703.87
  • Catalog: Vasopressin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Isoxsuprine hydrochloride

Isoxsuprine hydrochloride is a beta-adrenergic receptor agonist with Kis of 13.65 μΜ and 3.48 μΜ for myometrial and placcntal beta-adrenergic receptor, respectively. Isoxsuprine hydrochloride is also a NMDA receptor antagonist.

  • CAS Number: 579-56-6
  • MF: C18H24ClNO3
  • MW: 337.84100
  • Catalog: Adrenergic Receptor
  • Density: 1.146g/cm3
  • Boiling Point: 484.2ºC at 760mmHg
  • Melting Point: 203-204°
  • Flash Point: 246.6ºC

Efaroxan hydrochloride

Efaroxan hydrochloride is a potent and selective α2-adrenoceptor antagonist, antidiabetic activity. Efaroxan hydrochloride is a selective I1-Imidazoline receptor antagonist and can be used for the research of cardiovascular disease[1][2][3].

  • CAS Number: 89197-00-2
  • MF: C13H17ClN2O
  • MW: 252.740
  • Catalog: Adrenergic Receptor
  • Density: N/A
  • Boiling Point: 387ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 187.9ºC

Gluten Exorphin B5

Gluten Exorphin B5 is an exogenous opioid peptides derived from wheat gluten, acts on opioid receptor, increases postprandial plasma insulin level in rats[1].

  • CAS Number: 68382-18-3
  • MF: C30H38N6O7
  • MW: 594.66
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Substance P acetate salt

Substance P is a neuropeptide, acting as a neurotransmitter and as a neuromodulator.The endogenous receptor for substance P is neurokinin 1 receptor (NK1-receptor, NK1R). Sequence: Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2.

  • CAS Number: 33507-63-0
  • MF: C63H98N18O13S
  • MW: 1347.630
  • Catalog: Peptides
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Firazorexton

Firazorexton is a potent orexin type 2 receptor (OX2R) agonist (patent WO2019027058A1, example 395)[1].

  • CAS Number: 2274802-95-6
  • MF: C22H25F3N2O4S
  • MW: 470.51
  • Catalog: Orexin Receptor (OX Receptor)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DG5128

DG5128 is a preferential α2-adrenoceptor antagonist. DG5128 exhibits 7.4 times higher affinity (pKi=6.28) toward α2-adrenoceptor than α1-adrenoceptor.

  • CAS Number: 79689-25-1
  • MF: C16H19Cl2N3
  • MW: 324.24800
  • Catalog: Adrenergic Receptor
  • Density: N/A
  • Boiling Point: 460ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 232ºC

Dinoprostone

Prostaglandin E2 is a hormone-like substance that participate in a wide range of body functions such as the contraction and relaxation of smooth muscle, the dilation and constriction of blood vessels, control of blood pressure, and modulation of inflammation.

  • CAS Number: 363-24-6
  • MF: C20H32O5
  • MW: 352.465
  • Catalog: Prostaglandin Receptor
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 530.1±50.0 °C at 760 mmHg
  • Melting Point: 66-68 °C
  • Flash Point: 288.5±26.6 °C

Epinephrine bitartrate

L-Epinephrine bitartrate is an α-adrenergic and β-adrenergic receptor agonist. L-Epinephrine is a hormone secreted by the medulla of the adrenal glands.

  • CAS Number: 51-42-3
  • MF: C13H19NO9
  • MW: 333.291
  • Catalog: Adrenergic Receptor
  • Density: N/A
  • Boiling Point: 413.1ºC at 760 mmHg
  • Melting Point: ~155 °C (dec.)
  • Flash Point: 207.9ºC

Talipexole

Talipexole (B-HT920) is a dopamine agonist that has been proposed as an antiparkinsonian agent.Target: Dopamine ReceptorB-HT920 is a selective alpha 2-adrenoceptor agonist. The effects of B-HT920 have been specified using the alpha-adrenergic antagonists yohimbine and prazosin and the dopamine antagonist haloperidol. Yohimbine could not antagonize any of the actions of B-HT920. Pretreatment with prazosin showed a decrease in the loss of body weight caused by B-HT920, while pretreatment with yohimbine showed that B-HT920 induced an increased loss in body weight. These data suggest that B-HT920 under certain conditions exerts dopamine-agonistic actions in stimulating locomotor activity and alpha 1-adrenergic actions in inducing salivation and enhanced loss of body weight [1]. Concomitant treatment with talipexole, an anti-parkinsonian drug, inhibited MPTP-induced autolysis and individual death in a concentration-dependent manner. Pramipexole showed a similar protective effect. In addition, post-treatment with talipexole at 1 hr after MPTP completely inhibited MPTP-induced individual death. Although MPTP treatment caused 30% of the planarians to undergo autolysis and individual death within 12 hr, post-treatment with talipexole even at 12 hr completely rescued the remaining 70% of the planarians from death. These results suggest that the MPTP-treated planarian may be useful as a novel parkinsonian model in which talipexole has a protective effect even in the case of post-treatment [2].

  • CAS Number: 101626-70-4
  • MF: C10H15N3S
  • MW: 209.31
  • Catalog: Dopamine Receptor
  • Density: 1.167g/cm3
  • Boiling Point: 364.6ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 174.3ºC

naltrexone

Naltrexone is an antagonist of Opioid receptor. Naltrexone inhibits cell proliferation in vivo. Naltrexone reduces tumor growth by interfering with cell signalling and modifying the immune system[1].

  • CAS Number: 16590-41-3
  • MF: C20H23NO4
  • MW: 341.40
  • Catalog: Opioid Receptor
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 558.1±50.0 °C at 760 mmHg
  • Melting Point: 168-170ºC
  • Flash Point: 291.4±30.1 °C

Cenicriviroc

Cenicriviroc is an orally active, dual CCR2/CCR5 antagonist, also inhibits both HIV-1 and HIV-2, and displays potent anti-inflammatory and antiinfective activity.

  • CAS Number: 497223-25-3
  • MF: C41H52N4O4S
  • MW: 696.941
  • Catalog: HIV
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 913.5±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 506.3±34.3 °C

KRAS G12C inhibitor 51

KRAS G12C inhibitor 51 (example 1) is a KRAS G12C inhibitor[1].

  • CAS Number: 2762632-78-8
  • MF: C33H35FN6O3
  • MW: 582.67
  • Catalog: Ras
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Flibanserin D4

Flibanserin D4 is a deuterium labeled Flibanserin (BIMT-17). Flibanserin is a full agonist of the serotonin 5-HT1A receptor (Ki=1 nM) and an antagonist of 5-HT2A (49 nM)[1].

  • CAS Number: 2122830-90-2
  • MF: C20H17D4F3N4O
  • MW: 394.43
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Neuromedin N trifluoroacetate salt

Neuromedin N is a potent modulator of dopamine D2 receptor agonist binding in rat neostriatal membranes. Sequence: Lys-Ile-Pro-Tyr-Ile-Leu.

  • CAS Number: 92169-45-4
  • MF: C38H63N7O8
  • MW: 745.94900
  • Catalog: Peptides
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

norfenefrine

Norfenefrine is an orally active, endogenously found α-adrenergic agonist and can be used for the research of female stress incontinence[1][2].

  • CAS Number: 536-21-0
  • MF: C8H11NO2
  • MW: 153.178
  • Catalog: Adrenergic Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 360.7±27.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 172.0±23.7 °C

Tolazoline hydrochloride

Tolazoline(NSC35110; Imidaline) Hcl is a non-selective competitive α-adrenergic receptor antagonist.IC50 value:Target: α-adrenoceptor antagonistTolazoline can be synthesized by the heterocyclation of the ethyl ester of iminophenzylacetic acid with ethylene diamine, which forms the desired product. The structure of tolazoline is strikingly similar to α-adrenergic agonists, which are antiedema sympathomimetics.

  • CAS Number: 59-97-2
  • MF: C10H13ClN2
  • MW: 196.677
  • Catalog: Adrenergic Receptor
  • Density: 1.09g/cm3
  • Boiling Point: 338.2ºC at 760mmHg
  • Melting Point: 172-176 °C
  • Flash Point: 158.3ºC

Terlipressin Acetate

Terlipressin acetate is a vasopressin analogue with potent vasoactive properties. Terlipressin acetate is a highly selective vasopressin V1 receptor agonist that reduces the splanchnic blood flow and portal pressure and controlling acute variceal bleeding. Terlipressin acetate exerts anti-inflammatory and anti-oxidative effects. Terlipressin acetate has the potential for hepatorenal syndrome and norepinephrine-resistant septic shock treatment[1][2][3][4][5].

  • CAS Number: 914453-96-6
  • MF: C52H74N16O15S2.xC2H4O2
  • MW: 1347.476
  • Catalog: Vasopressin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ethybenztropine

Ethybenztropine (Ponalid) is a muscarinic receptor blocker. Ethybenztropine is an anticholinergic and antihistaminergic agent[1].

  • CAS Number: 524-83-4
  • MF: C22H27NO
  • MW: 321.45600
  • Catalog: mAChR
  • Density: 1.1g/cm3
  • Boiling Point: 422.8ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 124ºC

Irbesartan D4

Irbesartan D4 is the deuterium labeled Irbesartan, which is a highly potent and specific angiotensin II type 1 (AT1) receptor antagonist.

  • CAS Number: 1216883-23-6
  • MF: C25H24D4N6O
  • MW: 432.55400
  • Catalog: Angiotensin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Valsartan

Valsartan (CGP-48933) is an angiotensin II receptor antagonist for treatment of high blood pressure and heart failure.

  • CAS Number: 137862-53-4
  • MF: C24H29N5O3
  • MW: 435.519
  • Catalog: Angiotensin Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 684.9±65.0 °C at 760 mmHg
  • Melting Point: 116-117°C
  • Flash Point: 368.0±34.3 °C

Dopamine serotonin antagonist-1

Dopamine serotonin antagonist-1 is a dual dopamine and serotonin receptor antagonist with Kis of 200, 2500, 420, 39, 84, 40 nM for dopamine D1, D2,D4, and serotonin S2A, S2C, S3, respectively.

  • CAS Number: 1977-07-7
  • MF: C18H20N4
  • MW: 292.37800
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Amitraz

Amitraz is a non-systemic acaricide and insecticide, with alpha-adrenergic agonist activity, interaction with octopamine receptors of the central nervous system and inhibition of monoamine oxidases and prostaglandin synthesis.

  • CAS Number: 33089-61-1
  • MF: C19H23N3
  • MW: 293.406
  • Catalog: Adrenergic Receptor
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 450.7±55.0 °C at 760 mmHg
  • Melting Point: 86-87°C
  • Flash Point: 226.4±31.5 °C

Diprenorphine

Diprenorphine is a non-selective opioid antagonist with Ki values of 0.017, 0.072 and 0.23 nM against κ-, μ- and δ-opioid receptors, respectively[1]. Diprenorphine can be used for central poststroke pain (CPSP) research[1].

  • CAS Number: 14357-78-9
  • MF: C26H35NO4
  • MW: 425.56000
  • Catalog: Opioid Receptor
  • Density: 1.33 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

L-745870 trihydrochloride

L-745870 trihydrochloride is a potent, selective, brain-penetrant and orally active dopamine D4 receptor antagonist with a Ki of 0.43 nM. L-745870 trihydrochloride shows weaker affinity for D2 (Ki of 960 nM) and D3 (Ki of 2300 nM) receptors, and exhibits moderate affinity for 5-HT2 receptors, sigma sites and α-adrenoceptors[1][2][3].

  • CAS Number: 866021-03-6
  • MF: C18H20Cl2N4
  • MW: 363.28400
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A