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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Rolapitant Hydrochloride Monohydrate

Rolapitant hydrochloride hydrate (SCH619734 hydrochloride hydrate) is a potent, selective, long-acting and orally active neurokinin 1 (NK1) receptor antagonist with a Ki of 0.66 nM. Rolapitant hydrochloride hydrate does not interact with CYP3A4. Rolapitant hydrochloride hydrate shows potent anti-emetic activity in a ferret emesis model[1][2].

  • CAS Number: 914462-92-3
  • MF: C25H29ClF6N2O3
  • MW: 554.953
  • Catalog: Neurokinin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

UCSF678

UCSF678 is a 42 nM arrestin-biased partial agonist at the 5-HT5AR with a more restricted off-target profile and decreased assay liabilities. UCSF678 is a selective probe with which to study the function of the 5-HT5AR[1].

  • CAS Number: 2361697-55-2
  • MF: C15H18N2O2S
  • MW: 290.38
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Acyline

Acyline , a GnRH peptide analogue, is a GnRH antagonist that inhibits gonadotropin and testosterone (T) levels[1].

  • CAS Number: 170157-13-8
  • MF: C80H102ClN15O14
  • MW: 1533.211
  • Catalog: GNRH Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 1774.1±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 1026.7±34.3 °C

WAY-181187

WAY-181187 (SAX-187) is a potent and selective full 5-HT6 receptor agonist with a Ki of 2.2 nM and an EC50 of 6.6 nM[1]. WAY181187 mediates 5-HT6 receptor-dependent signal pathways, such as cAMP, Fyn and ERK1/2 kinase, as specific agonist[2].

  • CAS Number: 554403-49-5
  • MF: C15H13ClN4O2S2
  • MW: 380.87200
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ropinirole-d4 hydrochloride

Ropinirole-d4 (SKF 101468-d4) hydrochloride is the deuterium labeled Ropinirole hydrochloride. Ropinirole hydrochloride is a potent D3/D2 receptor agonist with a Ki of 29 nM for D2 receptor. Ropinirole hydrochloride has pEC50s of 7.4, 8.4 and 6.8 for hD2, hD3 and hD4 receptors, respectively. Ropinirole hydrochloride has no affinity for the D1 receptors. Ropinirole hydrochloride has the potential for Parkinson's disease[1][2].

  • CAS Number: 1330261-37-4
  • MF: C16H21D4ClN2O
  • MW: 300.86
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

glucagon monohydrochloride

Glucagon hydrochloride (Porcine glucagon hydrochloride) is a peptide hormone, produced by pancreatic α-cells. Glucagon hydrochloride stimulates gluconeogenesis[1]. Glucagon hydrochloride decreases the activity of HNF-4[2]. Glucagon hydrochloride increases HNF4α phosphorylation[3].

  • CAS Number: 28270-04-4
  • MF: C153H225N43O49S.ClH
  • MW: 3519.21
  • Catalog: Glucagon Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Leronlimab

Leronlimab (PRO 140) is a humanized IgG4 anti-CCR5 monoclonal antibody. Leronlimab inhibits CCR5-mediated HIV-1 viral and lung metastasis in mouse tumor models. Leronlimab can be used for the research of HIV nonalcoholic steatohepatitis (NASH) and cancer[1].

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

MK-886 (sodium salt)

MK-886 (L 663536) sodium salt is a potent, cell-permeable and orally active FLAP (IC50 of 30 nM) and leukotriene biosynthesis (IC50s of 3 nM and 1.1 μM in intact leukocytes and human whole blood, respectively) inhibitor. MK-886 sodium salt is also a non-competitive PPARα antagonist and can induce apoptosis[1][2][3].

  • CAS Number: 118427-55-7
  • MF: C27H33ClNNaO2S
  • MW: 494.06
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CP94253 hydrochloride

CP94253 hydrochloride is a potent and selective agonist of 5-HT1B receptor (Ki= 2 nM in a radioligand binding assay).Ki values for 5-HT1A, 5-HT1D, 5-HT1C and 5-HT2 receptors are 89, 49, 860, and 1600 nM respectively[1]. CP94253 hydrochloride is centrally active upon systemic administration in vivo[2].

  • CAS Number: 845861-39-4
  • MF: C15H20ClN3O
  • MW: 293.79200
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

N-[(4-Aminophenyl)methyl]adenosine

N-[(4-Aminophenyl)methyl]adenosine is a adenosine receptor inhibitor, with Ki of 29 nM for Rat ecto-5′-Nucleotidase.IC50 value: 29.0 ± 1.7 nM (Ki) Target: Adenosine Receptor

  • CAS Number: 95523-13-0
  • MF: C17H20N6O4
  • MW: 372.38
  • Catalog: Adenosine Receptor
  • Density: 1.71g/cm3
  • Boiling Point: 749ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 406.8ºC

Procaterol

Procaterol is an oral selective β2 adrenergic receptor agonist. Procaterol inhibits eosinophil migration and the release of eosinophil chemotactic factor from BEAS-2B cells through a cyclic AMP-dependent mechanism. Procaterol has a large dose difference existing between the bronchodilator effect and the anabolic effect in rat, can be used for asthma research in athletes[1].

  • CAS Number: 72332-33-3
  • MF: C16H22N2O3
  • MW: 290.36
  • Catalog: Adrenergic Receptor
  • Density: 1.191 g/cm3
  • Boiling Point: 539.5ºC at 760 mmHg
  • Melting Point: 170-173 °C(lit.)
  • Flash Point: N/A

AY77

AY77 is a calcium-biased PAR2 agonist. AY77 shows an EC50 of 0.17 and 2 nM in PAR2-mediated the activation in the Gq pathway and recruitment of β-arrestin-2, respectively. AY77 potently induces intracellular Ca2+ release[1][2].

  • CAS Number: 1835734-92-3
  • MF: C21H32N4O4
  • MW: 404.50
  • Catalog: Protease-Activated Receptor (PAR)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

naltrexone-d4

Naltrexone-d4 is deuterium labeled Naltrexone.

  • CAS Number: 2070009-29-7
  • MF: C20H19D4NO4
  • MW: 345.43
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MK-0354

MK-0354 is a partial agonist of GPR109a receptor, for hGPR109a/ mGPR109a with EC50 of 1.65/1.08 μM, showed no activation of GPR109b.IC50 value: 1.65 μM (EC50, for hGPR109a), 1.08 μM (EC50, for mGPR109a) [1]Target: GPR109ain vitro: MK-0354 demonstrated clear and statistically significant partial agonism in the cAMP assays for both the mouse and human receptors with efficacy approximately 60-70% of that of either nicotinic acid or β-hydroxy butyrate, a putative physiologically relevant ligand for hGPR109a, in the same assay platform. In addition, MK-0354 showed no activation of GPR109b in the cAMP assay at any concentration up to 100 μM. Following these interesting observations, we then prepared a number of other 5,5-fused pyrazoles analogous to those that showed receptor activity in our earlier studies. MK-0354 appeared to be somewhat unique among the members of the pyrazole tetrazole series in having reasonable receptor activity.[1]in vivo: MK-0354 retained the plasma free fatty acid lowering effects in mice associated with GPR109a agonism, but did not induce vasodilation at the maximum feasible dose. Moreover, preadministration of MK-0354 blocked the flushing effect induced by nicotinic acid but not that induced by PGD2. This profile made MK-0354 a suitable candidate for further study for the treatment of dyslipidemia.[1] MK-0354 is a GPR109A partial agonist that activates the antilipolytic pathway in adipocytes. The single-dose and multiple-dose pharmacokinetics and pharmacodynamics, as well as tolerability, of MK-0354 were examined in two Phase I studies conducted in healthy male volunteers. The lipid efficacy of MK-0354 was assessed in a Phase II study conducted in male and female patients with dyslipidemia.[2]

  • CAS Number: 851776-28-8
  • MF: C7H8N6
  • MW: 176.179
  • Catalog: GPR109A
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 535.3±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 273.9±25.8 °C

ST-836

ST-836 is a dopamine receptor ligand; Antiparkinsonian agent.

  • CAS Number: 1148156-63-1
  • MF: C23H34N4OS
  • MW: 414.60700
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

5-HT2A receptor agonist-3

5-HT2A receptor agonist-3 is the most selective agonist for the human 5-HT2A receptor yet discovered, with a Ki of 2.5 nM, and with 124-fold selectivity for 5-HT2A over the structurally similar 5-HT2C receptor[1].

  • CAS Number: 1391499-52-7
  • MF: C21H26BrNO3
  • MW: 420.34
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ac-hMCH(6–16)-NH2

Ac-hMCH(6-16)-NH2 binds to and activates equally well both human MCH receptors present in the brain (non-selective agonist), with IC50 values of 0.16 nM and 2.7 nM for MCH-1R and MCH-2R[1].

  • CAS Number: 1053601-50-5
  • MF: C58H99N21O13S3
  • MW: 1394.73
  • Catalog: MCHR1 (GPR24)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Spirendolol

Spirendolol is a β adrenergic receptor antagonist.

  • CAS Number: 81840-58-6
  • MF: C21H31NO3
  • MW: 345.48
  • Catalog: Adrenergic Receptor
  • Density: 1.12g/cm3
  • Boiling Point: 521.9ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 269.4ºC

(R)-(-)-α-Methylhistamine dihydrochloride

(R)-(-)-α-Methylhistamine dihydrochloride is a potent, selective and brain-penetrant agonist of H3 histamine receptor, with a Kd of 50.3 nM[1][2]. (R)-(-)-α-Methylhistamine dihydrochloride can enhance memory retention, attenuates memory impairment in rats[3][4][5].

  • CAS Number: 75614-89-0
  • MF: C6H13Cl2N3
  • MW: 198.09400
  • Catalog: Histamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Levodopa

L-DOPA is a natural form of DOPA used in the treatment of Parkinson's disease. L-DOPA is the precursor of dopamine and product of tyrosine hydroxylase.Target: Dopamine ReceptorL-DOPA (L-3,4-dihydroxyphenylalanine) is a chemical that is made and used as part of the normal biology of humans, some animals and plants. Some animals and humans make it via biosynthesis from the amino acid L-tyrosine. L-DOPA is the precursor to the neurotransmitters dopamine, norepinephrine (noradrenaline), and epinephrine collectively known as catecholamines. L-DOPA can be manufactured and in its pure form is sold as apsychoactive drug with the INN levodopa; trade names include Sinemet, Parcopa, Atamet, Stalevo, Madopar, Prolopa, etc. As a drug it is used in the clinical treatment of Parkinson's disease and dopamine-responsive dystonia.L-DOPA crosses the protective blood-brain barrier, whereas dopamine itself cannot. Thus, L-DOPA is used to increase dopamine concentrations in the treatment of Parkinson's disease and dopamine-responsive dystonia. This treatment was made practical and proven clinically by George Cotzias and his coworkers, for which they won the 1969 Lasker Prize. In addition, L-DOPA, co-administered with a peripheral DDCI, has been investigated as a potential treatment for restless leg syndrome. However, studieshave demonstrated "no clear picture of reduced symptoms".

  • CAS Number: 59-92-7
  • MF: C9H11NO4
  • MW: 197.188
  • Catalog: Dopamine Receptor
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 448.4±45.0 °C at 760 mmHg
  • Melting Point: 276-278 °C(lit.)
  • Flash Point: 225.0±28.7 °C

Bivamelagon hydrochloride

MC-4R Agonist 2 hydrochloride (Example 1) is a MC4R agonist. MC-4R Agonist 2 hydrochloride can be used in the study of obesity, diabetes, inflammation, and erectile dysfunction[1].

  • CAS Number: 2641595-55-1
  • MF: C35H54Cl2N4O4
  • MW: 665.73
  • Catalog: Inflammation/Immunology
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GnRH Associated Peptide: GAP: 1-13, human

GnRH Associated Peptide (GAP) (1-13), human is an amino acid peptide fragment derived from GnRH. GAP can increase the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in rat anterior pituitary cells. GAP also inhibit the secretion of prolactin[1].

  • CAS Number: 100111-07-7
  • MF: C65H101N15O25
  • MW: 1492.58000
  • Catalog: GNRH Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Metoprolol

Metoprolol (Toprol) is a selective β1 receptor blocker used in treatment of several diseases of the cardiovascular system, especially hypertension.IC50 value:Target: β1 receptor

  • CAS Number: 51384-51-1
  • MF: C15H25NO3
  • MW: 267.364
  • Catalog: Adrenergic Receptor
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 398.6±37.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 194.9±26.5 °C

VU 0238429

VU 0238429 is positive allosteric modulator of muscarinic acetylcholine receptor subtype 5 (mAChR5 or M5), with an EC50 of 1.16 μM.

  • CAS Number: 1160247-92-6
  • MF: C17H12F3NO4
  • MW: 351.27700
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Dynorphin A (1-10) acetate salt

Dynorphin A (1-10) an endogenous opioid neuropeptide, binds to extracellular loop 2 of the κ-opioid receptor. Dynorphin A (1-10) also blocks NMDA-activated current with an IC50 of 42.0 μM.

  • CAS Number: 79994-24-4
  • MF: C57H91N19O12
  • MW: 1234.45000
  • Catalog: Peptides
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

UCSF924

UCSF924 is a potent and specific dopamine D4 receptor (DRD4) partial agonist with a EC50 of 4.2 nM. UCSF924 has a high-affinity with a Ki value of 3 nM for DRD4 and shows no measurable affinity for D2, D3 or the F261V/L328F D4 mutant. UCSF924 is a 7.4-fold bias toward arrestin over Gαi/o signaling, referenced to quinpirole[1].

  • CAS Number: 1434515-70-4
  • MF: C20H22N2O2
  • MW: 322.40
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PAOPA

PAOPA, an analog of L-proline-l-leucine-glycine amide (PLG) peptide, is an allosteric modulator of Dopamine D2 Receptor. PAOPA can effectively reduce behavioral abnormalities in rodent models of schizophrenia. PAOPA increases the high affinity dopamine D2 receptor and promotes its binding to agonists[1].

  • CAS Number: 114200-31-6
  • MF: C11H18N4O3
  • MW: 254.28600
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Dexmedetomidine

Dexmedetomidine ((+)-Medetomidine) is a potent, selective and orally active agonist of α2-adrenoceptor, with a Ki of 1.08 nM. Dexmedetomidine shows 1620-fold selectivity against α1-adrenoceptor. Dexmedetomidine exhibits anxiolysis, sedation, and modest analgesia effects[1][2][3].

  • CAS Number: 113775-47-6
  • MF: C13H16N2
  • MW: 200.28000
  • Catalog: Adrenergic Receptor
  • Density: 1.053g/cm3
  • Boiling Point: 381.9ºC at 760mmHg
  • Melting Point: 146-149°C
  • Flash Point: 191.3ºC

AMD-070

AMD-070 is a potent, selective and orally available CXCR4 antagonist, with an IC50 value of 13 nM against CXCR4 125I-SDF binding, and also inhibits the replication of T-tropic HIV-1 (NL4.3 strain) in MT-4 cells and PBMCs with an IC50 of 1 and 9 nM, respectively.

  • CAS Number: 558447-26-0
  • MF: C21H27N5
  • MW: 349.473
  • Catalog: HIV
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 597.0±50.0 °C at 760 mmHg
  • Melting Point: 108-110ºC
  • Flash Point: 314.9±30.1 °C

CYT-1010

CYT-1010 is a mu-opioid receptor agonist extracted from patent WO2013173730A2, with EC50s of 13.1 nM and 0.0053 nM on beta-arrestin recruitment and inhibition of cAMP production, respectively[1].

  • CAS Number: 213769-33-6
  • MF: C35H40N6O5
  • MW: 624.73
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A