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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SB-242084

SB 242084 is a 5-HT2C receptor antagonist(pKi=9.0) that displays 158- and 100-fold selectivity over 5-HT2A and 5-HT2B receptors respectively.IC50 value: 9.0(pKi) [1]Target: 5-HT2C antagonistin vitro: SB 242084 had over 100-fold selectivity over a range of other 5-HT, dopamine and adrenergic receptors. In studies of 5-HT-stimulated phosphatidylinositol hydrolysis using SH-SY5Y cells stably expressing the cloned human 5-HT2C receptor, SB 242084 acted as an antagonist with a pKb of 9.3, which closely resembled its corresponding receptor binding affinity [1].in vivo: SB 242084 potently inhibited m-chlorophenylpiperazine (mCPP, 7 mgkg i.p. 20 min pre-test)-induced hypolocomotion in rats, a model of in vivo central 5-HT2C receptor function, with an ID50 of 0.11 mg/kg i.p., and 2.0 mg/kg p.o. SB 242084 (0.1-1 mg/kg i.p.) exhibited an anxiolytic-like profile in the rat social interaction test, increasing time spent in social interaction, but having no effect on locomotion. SB 242084 (0.1-1 mg/kg i.p.) also markedly increased punished responding in a rat Geller-Seifter conflict test of anxiety, but had no consistent effect on unpunished responding [1].

  • CAS Number: 181632-25-7
  • MF: C21H19ClN4O2
  • MW: 394.85
  • Catalog: 5-HT Receptor
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 620.1±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 328.8±31.5 °C

Orexin 2 Receptor Agonist

Orexin 2 Receptor Agonist is a potent (EC50 on OX2R is 23 nM) and OX2R-selective (OX1R/OX2R EC50 ratio is 70) agonist.IC50 value: 23 nM (EC50)Target: Orexin 2 ReceptorOrexin 2 Receptor Agonist shows not only potentactivity but also high selectivity for OX2R over OX1R. In CHO cells overexpressing hOX1R and HEK-293 cells overexpressing hOX2R, compound 26 displaced [125I]orexin-A in a concentration dependent manner: 26 bound to hOX2R and hOX1R with Ki of 0.14 and 0.77 μM, respectively.[1]

  • CAS Number: 1796565-52-0
  • MF: C32H34N4O5S
  • MW: 586.701
  • Catalog: Orexin Receptor (OX Receptor)
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cetrorelix Acetate

Cetrorelix Acetate is a potent gonadotropin-releasing hormone (GnRH) receptor antagonist with an IC50 of 1.21 nM. Sequence: N-acetyl-{2-Naph-Ala}-{Cl-Phe}-{3Py-Ala}-Ser-Tyr-{Cit}-Leu-Arg-Pro-Ala-NH2.

  • CAS Number: 145672-81-7
  • MF: C72H96ClN17O16
  • MW: 1491.09000
  • Catalog: Peptides
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Azilsartan mepixetil potassium

Azilsartan mepixetil potassium (QR-01019K) is the antagonist of angiotensin II receptor. Azilsartan mepixetil potassium has stronger and longer blood pressure effect, more abvious and longer lasting heart rate lowering effect and high safety. Azilsartan mepixetil potassium has the potential for the research of hypertension, chronic heart failure and diabetic nephropathy (extracted from patent CN107400122A)[1].

  • CAS Number: 2153458-32-1
  • MF: C36H33KN6O8
  • MW: 716.78
  • Catalog: Angiotensin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(R)-SLV 319

(R)-SLV 319 is a potent and selective cannabinoid receptor 1 (CB1) antagonist with a Ki value of 894 nM. (R)-SLV 319 is a dextrorotatory counterpart of SLV 319[1]

  • CAS Number: 656827-86-0
  • MF: C23H20Cl2N4O2S
  • MW: 487.40
  • Catalog: Cannabinoid Receptor
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 623.2±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 330.7±34.3 °C

Tolvaptan-d7

Tolvaptan-D7 (OPC-41061-D7) is the deuterium labeled Tolvaptan. Tolvaptan is a selective, competitive arginine vasopressin receptor 2 antagonist with an IC50 of 1.28μM for the inhibition of AVP-induced platelet aggregation[1][2].

  • CAS Number: 1246818-18-7
  • MF: C26H18D7ClN2O3
  • MW: 455.984
  • Catalog: Autophagy
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 594.4±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 313.3±30.1 °C

Clobetasone butyrate

Clobetasone butyrate is a synthetic glucocorticoid and has topical anti-inflammatory activity especially in skin. Clobetasone butyrate can be used to relieve corticosteroid-responsive dermatoses, including atopic dermatitis and psoriasis[1].

  • CAS Number: 25122-57-0
  • MF: C26H32ClFO5
  • MW: 478.981
  • Catalog: Glucocorticoid Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 573.3±50.0 °C at 760 mmHg
  • Melting Point: 179 °C
  • Flash Point: 181.1±19.3 °C

Tasipimidine sulfate

Tasipimidine sulfate is an orally active and selective α2A-adrenoceptor agonist with a pEC50 of 7.57 against human α2A-adrenoceptor. Tasipimidine sulfate can be used for situational anxiety and fear research[1].

  • CAS Number: 1465908-73-9
  • MF: C13H18N2O6S
  • MW: 330.36
  • Catalog: Adrenergic Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Lu AE58054 (Hydrochloride)

Idalopirdine Hydrochloride (Lu AE58054 Hydrochloride) is a potent and selective 5-HT6 receptor antagonist with a Ki of 0.83 nM.

  • CAS Number: 467458-02-2
  • MF: C20H20ClF5N2O
  • MW: 434.831
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Falintolol, (Z)-

Falintolol, (Z)-, a new β-adrenergic antagonist, is characterized by the presence of an oxime function.

  • CAS Number: 106401-52-9
  • MF: C12H24N2O2
  • MW: 228.331
  • Catalog: Adrenergic Receptor
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 343.6±52.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 161.6±30.7 °C

TSHR antagonist S37

TSHR antagonist S37 is a selective and competitive thyrotropin receptor (TSHR) antagonist. TSHR antagonist S37 is the racemate of TSHR antagonist S37a[1].

  • CAS Number: 1217616-61-9
  • MF: C25H20N2O3S2
  • MW: 460.57
  • Catalog: TSH Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AP102

AP102 is a dual SSTR2/SSTR5-specific somatostatin analog (SSA). AP102 is a disulfide-bridged octapeptide SSA containing synthetic iodinated amino acids. AP102 binds with subnanomolar affinity to SSTR2 and SSTR5 (IC50: 0.63 and 0.65 nM, respectively). AP102 does not bind to SSTR1 or SSTR3. AP102 can be used for acromegaly and neuroendocrine tumors research[1].

  • CAS Number: 846569-60-6
  • MF: C50H66I2N12O10S2
  • MW: 1313.07
  • Catalog: Somatostatin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Fananserin

Fananserin (RP 62203) is an orally bioavailable, potent and selective 5-hydroxytryptamine2 (5-HT2) receptor antagonist, with a Ki of 0.37 nM for the rat 5-HT2A receptor. Fananserin also is a selective dopamine D4 receptor antagonist, with a Ki of 2.93 nM for the human dopamine D4 receptor[1].

  • CAS Number: 127625-29-0
  • MF: C23H24FN3O2S
  • MW: 425.51900
  • Catalog: 5-HT Receptor
  • Density: 1.331g/cm3
  • Boiling Point: 641.1ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 341.5ºC

DETQ

A novel potent, selective, allosteric and orally active dopamine D1 receptor potentiator with Kb of 26 nM; induces a 21-fold leftward shift in the cAMP response to dopamine in HEK293 cells, 30-fold less potent at rat and mouse D1 receptors and is inactive at the human D5 receptor; robustly (∼10-fold) increases locomotor activity in habituated hD1 mice (3-20 mg/kg), also acts synergistically with L-DOPA to reverse the strong hypokinesia caused by reserpine.

  • CAS Number: 1638667-81-8
  • MF: C22H25Cl2NO3
  • MW: 422.346
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Naloxone

Naloxone is an antagonist of Opioid receptor. Naloxone alleviates opioid-overdose-induced respiratory depression. Naloxone may cause pulmonary edema and cardiac arrhythmias[1].

  • CAS Number: 465-65-6
  • MF: C19H21NO4
  • MW: 327.37
  • Catalog: Opioid Receptor
  • Density: 1.43 g/cm3
  • Boiling Point: 532.8ºC at 760 mmHg
  • Melting Point: 184ºC
  • Flash Point: 276.1ºC

SCH 79797 dihydrochloride

SCH79797 dihydrochloride is a highly potent, selective nonpeptide protease activated receptor 1 (PAR1) antagonist. SCH79797 dihydrochloride inhibits binding of a high-affinity thrombin receptor-activating peptide to PAR1 with an IC50 of 70 nM and a Ki of 35 nM. SCH79797 dihydrochloride inhibits thrombin-induced platelet aggregation with an IC50 of 3 μM. SCH79797 dihydrochloride has antiproliferative and pro-apoptotic effects, and limits myocardial ischemia/reperfusion injury in rat hearts. SCH79797 dihydrochloride also potently prevents PAR1 activation in vascular smooth muscle cells, endothelial cells, and astrocytes[1][2][3][4].

  • CAS Number: 1216720-69-2
  • MF: C23H27Cl2N5
  • MW: 444.400
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Triamcinolone

Triamcinolone is a long-acting synthetic corticosteroid.Target: Glucocorticoid ReceptorDimethyl fumarate is an anti-inflammatory. It is indicated for multiple sclerosis patients with relapsing forms and is also being investigated for the treatment of psoriasis. The mechanism of action of dimethyl fumarate in multiple sclerosis is not well understood. It is thought to involve dimethyl fumarate degradation to its active metabolite monomethyl fumarate (MMF) then MMF up-regulates the Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway that is activated in response to oxidative stress [1]. The mean duration of follow-up was 40 months. The rate of decline in the FEV1 after bronchodilator use was similar in the 559 participants in the triamcinolone group and the 557 participants in the placebo group (44.2+/-2.9 vs. 47.0+/-3.0 ml per year, P= 0.50). Members of the triamcinolone group had fewer respiratory symptoms during the course of the study (21.1 per 100 person-years vs. 28.2 per 100 person-years, P=0.005) and had fewer visits to a physician because of a respiratory illness (1.2 per 100 person-years vs. 2.1 per 100 person-years, P=0.03). Those taking triamcinolone also had lower airway reactivity in response to methacholine challenge at 9 months and 33 months (P=0.02 for both comparisons) [2].

  • CAS Number: 124-94-7
  • MF: C21H27FO6
  • MW: 394.434
  • Catalog: Bacterial
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 587.5±50.0 °C at 760 mmHg
  • Melting Point: 262-263 °C(lit.)
  • Flash Point: 309.1±30.1 °C

5-HT3 antagonist 1

5-HT3 antagonist 1 is a potent and selective antagonist of serotonin 3 (5-HT3) receptor.

  • CAS Number: 129294-09-3
  • MF: C22H27N5O
  • MW: 377.48300
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Terbutaline sulfate

Terbutaline sulfate is a β2-adrenergic receptor agonist; a fast-acting bronchodilator and a tocolytic to delay premature labor.

  • CAS Number: 23031-32-5
  • MF: C12H19NO3.1/2H2O4S
  • MW: 274.32
  • Catalog: Adrenergic Receptor
  • Density: 1.1840 (rough estimate)
  • Boiling Point: 419.2ºC at 760 mmHg
  • Melting Point: 246-248ºC
  • Flash Point: 165.3ºC

Quetiapine hemifumarate-d8

Quetiapine (hemifumarate)-d8 is the deuterium labeled Quetiapine hemifumarate[1]. Quetiapine hemifumarate is a 5-HT receptors agonist with a pEC50 of 4.77 for human 5-HT1A receptor. Quetiapine hemifumarate is a dopamine receptor antagonist with a pIC50 of 6.33 for human D2 receptor. Quetiapine hemifumarate has moderate to high affinity for the human D2, HT1A, 5-HT2A, 5-HT2C receptor with pKis of 7.25, 5.74, 7.54, 5.55. Antidepressant and anxiolytic effects[2].

  • CAS Number: 1435938-24-1
  • MF: (C21D8H17N3O2S)2·C4H4O4
  • MW: 899.18
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

KP136

KP136 is an orally effective antiallergic agent. The IC50 is 76.1 μg/mL for histamine release and 63 ug/mL for degranulation.

  • CAS Number: 76239-32-2
  • MF: C16H18N4O3
  • MW: 314.33900
  • Catalog: Histamine Receptor
  • Density: 1.289g/cm3
  • Boiling Point: 556.9ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 290.6ºC

Lofexidine

Lofexidine is a selective α2-receptor agonist, commonly used to alleviate the physical symptoms of heroin and other types of opioid withdrawal[1][2].

  • CAS Number: 31036-80-3
  • MF: C11H12Cl2N2O
  • MW: 259.132
  • Catalog: Adrenergic Receptor
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 421.5±35.0 °C at 760 mmHg
  • Melting Point: 215-225 °C
  • Flash Point: 208.7±25.9 °C

Macitentan

Macitentan is an orally active, non-peptide endothelin receptor antagonist for the treatment of idiopathic pulmonary fibrosis and pulmonary arterial hypertension.

  • CAS Number: 441798-33-0
  • MF: C19H20Br2N6O4S
  • MW: 588.27
  • Catalog: Endothelin Receptor
  • Density: 1.7±0.1 g/cm3
  • Boiling Point: 692.4±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 372.5±34.3 °C

Cimetropium bromide

Cimetropium Bromide is a mAChR antagonist for long-term treatment of irritable bowel syndrome.

  • CAS Number: 51598-60-8
  • MF: C21H28BrNO4
  • MW: 438.35500
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

LY2940094

LY2940094 is a potent, selective and orally available nociceptin receptor (NOP) antagonist with an Ki of 0.105 nM.

  • CAS Number: 1307245-86-8
  • MF: C22H23ClF2N4O2S
  • MW: 480.96
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Flibanserin hydrochloride

Flibanserin (BIMT-17; BIMT-17BS) hydrochloride is an orally active serotonin 5-HT1A receptor agonist and 5-HT2A receptor antagonist with Ki values of 1 nM and 49 nM, respectively. Flibanserin hydrochloride binds to dopamine D4 receptors with an Ki value of 4-24 nM. Flibanserin hydrochloride shows anti-depression and anti-anxiety effect, can be used to hypoactive sexual desire disorder (HSDD) research[1]-[5].

  • CAS Number: 147359-76-0
  • MF: C20H22ClF3N4O
  • MW: 426.863
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: >225°C (dec.)
  • Flash Point: N/A

Tulobuterol hydrochloride

Tulobuterol hydrochloride is a β2-adrenoceptor agonist.

  • CAS Number: 56776-01-3
  • MF: C12H19Cl2NO
  • MW: 264.191
  • Catalog: Adrenergic Receptor
  • Density: 1.098 g/cm3
  • Boiling Point: 338.2ºC at 760 mmHg
  • Melting Point: 163ºC
  • Flash Point: 158.3ºC

Haloperidol D4

Haloperidol D4 is deuterium labeled haloperidol, and the latter is a potent dopamine D2 receptor antagonist.

  • CAS Number: 1189986-59-1
  • MF: C21H19D4ClFNO2
  • MW: 379.889
  • Catalog: Dopamine Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 529.0±50.0 °C at 760 mmHg
  • Melting Point: 148-1500C
  • Flash Point: 273.8±30.1 °C

L-Glutamine-15N-1

L-Glutamine-15N-1 (L-Glutamic acid 5-amide-15N-1) is the 15N-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: 59681-32-2
  • MF: C5H10N15NO3
  • MW: 146.145
  • Catalog: Ferroptosis
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 445.6±40.0 °C at 760 mmHg
  • Melting Point: 185ºC (dec.)(lit.)
  • Flash Point: 223.3±27.3 °C

angiopeptin

Angiopeptin, a cyclic octapeptide analogue of somatostatin, markedly inhibits myointimal proliferation in response to endothelial cell injury. Angiopeptin is a potent and full agonists to inhibit adenylate cyclase or stimulate extracellular acidification through the sst2 or sst5 receptor. Angiopeptin is a potent inhibitor of growth hormone release and insulin-like growth factor-1 production[1][2].

  • CAS Number: 113294-82-9
  • MF: C54H71N11O10S2
  • MW: 1098.339
  • Catalog: Somatostatin Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 1502.5±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 862.5±34.3 °C