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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SKF-83822

SKF 83822 is an atypical agonist of dopamine D1 receptor. SKF 83822 activates adenylyl cyclase, but not PLC. SKF 83822 is also proved to stimulate AC via cAMP production. SKF 83822 can be used for research of schizophrenia[1][2].

  • CAS Number: 74115-08-5
  • MF: C20H22ClNO2
  • MW: 343.85
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

adrenaline sulfate

Adrenaline sulfate is a orally active hormone secreted by the medulla of the adrenal glands. Adrenaline sulfate is an α-adrenergic and β-adrenergic receptor agonist. Adrenaline sulfate can be used in the treatment of anaphylaxis. Adrenaline sulfate has the potential for the research of cardiac arrest[1][2][3][4].

  • CAS Number: 52455-32-0
  • MF: C12H18O3
  • MW: 210.270
  • Catalog: Adrenergic Receptor
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 301.3±42.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 129.0±27.9 °C

Prostaglandin B1

Prostaglandin B1 (PGB1) is a metabolite of Prostaglandin E1 (HY-B0131). Prostaglandin E1 is a prostanoid receptor ligand[1][2].

  • CAS Number: 13345-51-2
  • MF: C20H32O4
  • MW: 336.47
  • Catalog: Prostaglandin Receptor
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 531.4±43.0 °C at 760 mmHg
  • Melting Point: 69-71°C(lit.)
  • Flash Point: 289.2±24.7 °C

JTC-017

JTC-017, a specific corticotropin-releasing hormone receptor 1 antagonist, attenuates hippocampal noradrenaline release, visceral perception, adrenocorticotropic hormone release, and anxiety after acute colorectal distention in rats. JTC-017 blocks stress-induced changes in colonic motility after chronic colorectal distention in rats[1].

  • CAS Number: 357330-77-9
  • MF: C20H25Cl2N3O5S
  • MW: 490.40100
  • Catalog: CRFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AM-6538

AM-6538 (AM6538) is a potent, selective cannabinoid receptor CB1 antagonist with Ki of 5.1 nM.

  • CAS Number: 1245626-00-9
  • MF: C26H25Cl2N5O4
  • MW: 542.417
  • Catalog: Cannabinoid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(4E)-SUN9221

(4E)-SUN9221 is a potent antagonist of α1-adrenergic receptor and 5-HT2 receptor, with antihypertensive and anti-platelet aggregation activities.

  • CAS Number: 222318-55-0
  • MF: C25H31FN4O3
  • MW: 454.54
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PZ-1190

PZ-1190 is a multitarget ligand for serotonin and dopamine receptors with potential antipsychotic activity in rodents[1].

  • CAS Number: 1852517-78-2
  • MF: C27H30N4O2S2
  • MW: 506.68
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ziprasidone D8

Ziprasidone D8 is deuterium labeled Ziprasidone, which is a combined 5-HT (serotonin) and dopamine receptor antagonist which exhibits potent effects of antipsychotic activity.

  • CAS Number: 1126745-58-1
  • MF: C21H13D8ClN4OS
  • MW: 420.98
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Vilanterol

Vilanterol is a long-acting β2-adrenoceptor (β2-AR) agonist with 24 h activity. The pEC50s for β2-AR,β1-AR and β3-AR is 10.37±0.05, 6.98±0.03 and 7.36±0.03, respectively.

  • CAS Number: 503068-34-6
  • MF: C24H33Cl2NO5
  • MW: 486.428
  • Catalog: Adrenergic Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 646.7±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 344.9±31.5 °C

Naftopidil

Naftopidil (Flivas), a selective α1-adrenergic receptor antagonist or alpha blocker, is an antihypertensive drug.Target: α1-Adrenergic ReceptorNaftopidil significantly improved the overall international prostatic symptom score ; from 19.2±7.9 to 11.7±5.8 in the M group and from 19.4±6.4 to 12.3±6.8 in the E group (p<0.0001), QOL score from 4.9±0.8 to 3.2±1.4 in the M group and from 5.0±0.8 to 3.6±1.3 in the E group (p<0.0001), and OAB symptom score from 7.8±2.6 to 5.0±2.5 in the M group (p<0.0001) and from 8.6±2.9 to 5.8± 3.3 in the E group (p<0.0001). naftopidil improves storage symptoms as well as voiding symptoms regardless of timing of administration [1]. The selectivity of naftopidil for prostatic pressure was the most potent among the test compounds. In addition, using cloned human alpha1-adrenoceptor subtypes, naftopidil was selective for the alpha1d-adrenoceptor with approximately 3- and 17-fold higher affinity than for the alpha1a- and alpha1b-adrenoceptor subtypes, respectively. The selectivity of naftopidil for prostatic pressure may be attributable to its high binding affinity for alpha1a- and alpha1d-adrenoceptor subtypes [2].

  • CAS Number: 57149-07-2
  • MF: C24H28N2O3
  • MW: 392.491
  • Catalog: Adrenergic Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 602.8±55.0 °C at 760 mmHg
  • Melting Point: 127 °C
  • Flash Point: 318.3±31.5 °C

Mast Cell Degranulating (MCD) Peptide

Peptide 401, a potent mast cell degranulating factor from bee venom, suppresses the increased vascular permeability due to intradermal injection of various smooth muscle spasmogens (histamine, and 5-HT).

  • CAS Number: 32908-73-9
  • MF: C110H192N40O24S4
  • MW: 2587.22000
  • Catalog: Peptides
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(R)?-?PIA

(-)-N6-phenylisopropyl adenosine (D-phenylisopropyladenosine) is a adenosine receptor agonist. (-)-N6-phenylisopropyl adenosine inhibits K+-evoked Ca2+ uptake with an IC50 value of 0.5 µM[1].

  • CAS Number: 38594-96-6
  • MF: C19H23N5O4
  • MW: 385.42
  • Catalog: Adenosine Receptor
  • Density: 1.506g/cm3
  • Boiling Point: 675.716ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 362.46ºC

vMIP-II (1-21)

vMIP-II (1-21) is a CXCR4 antagonist. vMIP-II has broad-spectrum interaction with CC and CXC chemokine receptors. vMIP-II (1-21) binds with CXCR4 with an IC50 value of 190 nM for competing with CXCR4 binding of 125I-SDF-1R[1].

  • CAS Number: 265650-93-9
  • MF: C108H169N33O27S
  • MW: 2425.84
  • Catalog: CXCR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

KRAS G12C inhibitor 47

KRAS G12C inhibitor 47 (compound 8-1-1) is a potent KRAS G12C inhibitor with an IC50 of 0.172 µM. KRAS G12C inhibitor 47 shows p-ERK inhibition activities with IC50s of 0.046, 69.8 µM in MIA PaCA-2, A549 cells, respectively. KRAS G12C inhibitor 47 has the potential for the research of pancreatic, colorectal, and lung cancers[1].

  • CAS Number: 2253119-24-1
  • MF: C30H28ClFN4O3
  • MW: 547.02
  • Catalog: Ras
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

WAY-100635

WAY-100635 is a potent and selective 5-HT1A Receptor antagonist with a pIC50 of 8.87, an apparent pA2 of 9.71.

  • CAS Number: 162760-96-5
  • MF: C25H34N4O2
  • MW: 422.56300
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Suntinorexton

Suntinorexton, a heterocyclic compound, is an orexin type 2 receptor agonist extracted from patent WO2019027058A1, page 288[1].

  • CAS Number: 2274802-89-8
  • MF: C23H28F2N2O4S
  • MW: 466.54
  • Catalog: Orexin Receptor (OX Receptor)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ZD 7155 hydrochloride

ZD 7155 hydrochloride is an angiotensin II receptor type 1 (AT1 receptor) antagonist.

  • CAS Number: 146709-78-6
  • MF: C26H27ClN6O
  • MW: 474.98500
  • Catalog: Angiotensin Receptor
  • Density: N/A
  • Boiling Point: 746.4ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 405.2ºC

[3-(quinolin-2-ylmethoxy)phenyl]methanol

CAY10789 (compound 6) is a potent CysLT1R (cysteinyl leukotriene receptor 1) antagonist (IC50=2.80 μM) and GPBAR1 (G-protein-coupled bile acid receptor 1) agonist (EC50=3 μM). CAY10789 significantly reduces the adhesion of U937 cells to HAEC, reduces the expression of TNF-α. CAY10789 shows very promising metabolic stability and excellent pharmacokinetics. CAY10789 can be used for the research of colitis, metabolic syndromes, and other GPBAR1/CysLT1R-related diseases[1].

  • CAS Number: 123226-28-8
  • MF: C17H15NO2
  • MW: 265.30700
  • Catalog: GPCR19
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MHP 133

HY-101653 is a drug with multiple CNS targets, and inhibits acetylcholinesterase (AChE) with Ki of 69 μM; also active against muscarinic M1 and M2 receptors, serotonin 5HT4 receptors, and imidazole I2 receptors.

  • CAS Number: 147340-43-0
  • MF: C17H20ClN5O3
  • MW: 377.825
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(R)-Casopitant

(R)-Casopitant ((R)-GW679769) is the isomer of Casopitant (HY-14405). Casopitant is a NK(1)-receptor antagonist. Casopitant can be used for the research of chemotherapy-induced nausea and vomiting[1][2].

  • CAS Number: 414910-26-2
  • MF: C30H35F7N4O2
  • MW: 616.61
  • Catalog: Neurokinin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ivabradine (D3 Hydrochloride)

Ivabradine D3 Hydrochloride is the deuterium labeled Ivabradine hydrochloride. Ivabradine hydrochloride is a new If inhibitor with IC50 of 2.9 μM, and used as a pure heart rate lowering agent.

  • CAS Number: 1217809-61-4
  • MF: C27H34D3ClN2O5
  • MW: 508.06
  • Catalog: Adrenergic Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(R)-3-O-Methyldopa-d3 hydrochloride

(R)-3-O-Methyldopa-d3 hydrochloride is a deuterium labeled (R)-3-O-Methyldopa, and (R)-3-O-Methyldopa is an R-enantiomer of 3-O-Methyldopa. 3-O-Methyldopa is a metabolite of L-DOPA which is formed by catechol-O-methyltransferase (COMT). 3-O-Methyldopa competitively inhibits the pharmacodynamics of L-DOPA and dopamine[1][2].

  • CAS Number: 2714485-35-3
  • MF: C10H11D3ClNO4
  • MW: 250.69
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NK3R-IN-1

NK3R-IN-1 (compound 16x), a imidazolepiperazine derivative, is an orally active Neurokinin Receptor NK3R inhibitor. NK3R-IN-1 decreases blood luteinizing hormone levels in ovariectomy (OVX) model[1].

  • CAS Number: 2854331-14-7
  • MF: C17H16FN5OS
  • MW: 357.41
  • Catalog: Neurokinin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bisoprolol

Bisoprolol is a potent, selective and orally active β1-adrenergic receptor blocker. Bisoprolol has little activity on β2-receptor and has the potential for hypertension, coronary artery disease and stable ventricular dysfunction research[1][2].

  • CAS Number: 66722-44-9
  • MF: C18H31NO4
  • MW: 325.443
  • Catalog: Adrenergic Receptor
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 445.0±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 222.9±28.7 °C

Nemorexant

Nemorexant is a potent orexin receptor antagonist extracted from patent WO2015083094A1, compound example 7, has IC50s of 2 nM and 3 nM for Ox1 receptor and Ox2 receptor, respectively.

  • CAS Number: 1505484-82-1
  • MF: C23H23ClN6O2
  • MW: 450.921
  • Catalog: Orexin Receptor (OX Receptor)
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 747.6±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 405.9±35.7 °C

OX2R-IN-1

OX2R-IN-1 is a low cytotoxicity profile OX2R-IN-1 antagonist (a potential OX2R binder) with an IC50 value of 484 μM. OX2R-IN-1 can cross the BBB into the brain with a short half-life[1].

  • CAS Number: 2639148-08-4
  • MF: C20H28ClN3O5S
  • MW: 457.97
  • Catalog: Orexin Receptor (OX Receptor)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Granuliberin-R

Granuliberin R is a new mast cell degranulating peptide comes from amphibian, can be isolated from the skin of frog Rana rugosa. Granuliberin R is a dodecapeptide, can act on rat peritoneal mast cell to liberate granules and release histamine[1][2].

  • CAS Number: 64704-41-2
  • MF: C69H103N19O14
  • MW: 1422.68000
  • Catalog: Histamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Isometheptene Mucate

Isometheptene mucate, a sympathomimetic agent, is a indirect-acting adrenergic receptor agonist. Isometheptene mucate can be used for migraine research[1].

  • CAS Number: 7492-31-1
  • MF: C21H39NO16
  • MW: 561.53100
  • Catalog: Adrenergic Receptor
  • Density: N/A
  • Boiling Point: 706.9ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 381.3ºC

Tradipitant

Tradipitant is a neurokinin-1 (NK-1) antagonist.

  • CAS Number: 622370-35-8
  • MF: C28H16ClF6N5O
  • MW: 587.903
  • Catalog: Neurokinin Receptor
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 640.9±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 341.4±34.3 °C

BRL-54443

BRL 54443 is a potent 5-HT1E/1F receptor agonist (pKi values are 8.7 and 8.9 respectively); displays > 30-fold selectivity over other 5-HT and dopamine receptors.IC50 value: 8.7(pKi, 5-HT1E); 8.9 (pKi, 5-HT1F) Target: 5-HT1E/1F receptorin vitro: BRL 54443 is a potent 5-ht1E/1F receptor agonist (pEC50 values are 8.5 and 8.6 respectively). Displays > 30-fold selectivity over other 5-HT and dopamine receptors (pKi values are 8.7. 8.9, 7.2, 6.9, 7.2, 5.9, 7.0, 6.5, < 6, < 6, 6.3 and 6.2 for human 5-HT1E, 1F, 1A, 1B, 1D, 2A, 2B, 2C, 4, 7, D2 and D3 receptors respectively). Induces 5-HT2A receptor-mediated mouse aortic contraction in vitro (pEC50 = 6.52). Active in vivo. In DG membranes, BRL54443, a 5-ht(1E) /5-HT(1F) agonist, selectively stimulated 5-ht(1E) receptors and potently inhibited forskolin-dependent cAMP production (IC50 = 14 nM) [2]. The 5-HT(1E/1F) receptor agonist BRL 54443 also induced contraction (-log EC(50) = 6.52) [1].in vivo: Reduction of flinching was considered as antinociception. Ipsilateral, but not contralateral, peripheral administration of BRL54443 (5-HT(1E/1F); 3-300 microg/paw) significantly reduced formalin-induced flinching in rats [3].

  • CAS Number: 57477-39-1
  • MF: C14H18N2O
  • MW: 230.305
  • Catalog: 5-HT Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 431.5±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 214.8±28.7 °C