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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Harmine

Harmine is a natural dual-specificity tyrosine phosphorylation-regulated kinase ((DYRK)) inhibitor with anticancer and anti-inflammatory activities.

  • CAS Number: 442-51-3
  • MF: C13H12N2O
  • MW: 212.247
  • Catalog: RAD51
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 421.4±40.0 °C at 760 mmHg
  • Melting Point: 262-264 °C(lit.)
  • Flash Point: 139.8±17.0 °C

SOS1/KRAS-IN-1

SOS1/KRAS-IN-1(Compound 2) is a SOS1/KRAS inhibitor, which can be used in the research of SOS1/KRAS-mediated diseases[1].

  • CAS Number: 2836330-34-6
  • MF: C24H26F3N5O
  • MW: 457.49
  • Catalog: Ras
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Dopamine hydrochloride

Dopamine HCl is a catecholamine neurotransmitter present in a wide variety of animals,And a dopamine D1-5 receptors agonist.Target: Dopamine ReceptorDopamine (or 3,4-dihydroxyphenethylamine) is a neuroendocrine transmitter in the catecholamine and phenethylamine families that plays a number of important roles in the brain and bodies of humans. Several important diseases of the nervous system are associated with dysfunctions of the dopamine system. Outside the nervous system, dopamine functions in several parts of the body as a local chemical messenger. In the blood vessels, it inhibits norepinephrine release and acts as a vasodilator; in the kidneys, it increases sodium excretion and urine output; in the pancreas, it reduces insulin production; in the digestive system, it reduces gastrointestinal motility and protects intestinal mucosa; and in the immune system, it reduces the activity of lymphocytes. A variety of important drugs work by altering the way the body makes or uses dopamine. Dopamine itself is available for intravenous injection: although it cannot reach the brain from the bloodstream, its peripheral effects make it useful in the treatment of heart failure or shock, especially in newborn babies. L-DOPA, the metabolic precursor of dopamine, does reach the brain and is the most widely used treatment for Parkinson's disease. From Wikipedia.

  • CAS Number: 62-31-7
  • MF: C8H12ClNO2
  • MW: 189.639
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: 337.7ºC at 760 mmHg
  • Melting Point: 248-250 °C(lit.)
  • Flash Point: N/A

MTEP

MTEP is a potent, non-competitive and highly selective mGluR5 antagonist, with an IC50 of 5 nM and a Ki of 16 nM. MTEP shows antidepressant and anxiolytic-like effects. MTEP can be used for Parkinson's disease research[1][2][3][4].

  • CAS Number: 329205-68-7
  • MF: C11H8N2S
  • MW: 200.26000
  • Catalog: mGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

oleoylglycine

N-Oleoyl glycine is a lipoamino acid, which stimulates adipogenesis associated with activation of CB1 receptor and Akt signaling pathway in 3T3-L1 adipocyte.

  • CAS Number: 2601-90-3
  • MF: C20H37NO3
  • MW: 339.513
  • Catalog: Cannabinoid Receptor
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 525.6±43.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 271.7±28.2 °C

Paroxetine

Paroxetine, a phenylpiperidine derivative, is a potent and selective serotonin reuptake inhibitor (SSRI). Paroxetine is a very weak inhibitor of norepinephrine (NE) uptake but it is still more potent at this site than the other SSRIs[1].

  • CAS Number: 61869-08-7
  • MF: C19H20FNO3
  • MW: 329.365
  • Catalog: Adrenergic Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 451.7±45.0 °C at 760 mmHg
  • Melting Point: 114-116°C
  • Flash Point: 227.0±28.7 °C

UNII:76LB1G2X6V

MK-571 (L-660711) is an orally active, potent and selective competitive leukotriene D4 (LTD4) receptor antagonist, with Ki values of 0.22 and 2.1 nM in guinea pig and human lung membranes, respectively. MK-571 is also a MRP4 and ABCC1 (MRP1) inhibitor. MK-571 inhibits constitutive and antigen-stimulated S1P (sphingosine-1-phosphate) release[1][2][3].

  • CAS Number: 115104-28-4
  • MF: C26H27ClN2O3S2
  • MW: 515.09
  • Catalog: Leukotriene Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 712.3±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 384.6±32.9 °C

INCB13739

INCB13739 is an orally active, potent, selective and tissue-specific11β-HSD1 (11β-hydroxysteroid dehydrogenase 1) inhibitor, with IC50 values of 3.2 nM (11β-HSD1 enzymatic) and 1.1 nM (11β-HSD1 PBMC), respectively. INCB13739 can be used for type 2 diabetes mellitus (T2DM) and obesity research[1].

  • CAS Number: 869974-19-6
  • MF: C28H25N3O4
  • MW: 467.52
  • Catalog: Glucocorticoid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MK-8768

MK-8768 is a highly potent, orally bioavailable and selective class of mGluR2 negative allosteric modulator (IC50 of 9 .6nM) with excellent brain permeability.

  • CAS Number: 1432729-22-0
  • MF: C21H22F3N5O2
  • MW: 433.43
  • Catalog: mGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

L-755,507

L755507 is a potent, selective agonist of β3-AR with an IC50 of 35 nM.

  • CAS Number: 159182-43-1
  • MF: C30H40N4O6S
  • MW: 584.727
  • Catalog: Adrenergic Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Nebentan free base

Nebentan (YM598) is a potent, selective and orally active non-peptide endothelin ETA receptor antagonist through the modification of Bosentan (HY-A0013). Nebentan inhibits [125I] endothelin-1 binding to cloned human endothelin ETA and ETB receptor, with Ki of 0.697 nM and 569 nM, respectively[1]. YM598 can ameliorate the progression of cor pulmonale and myocardial infarction in vivo[2].

  • CAS Number: 403604-85-3
  • MF: C24H21N5O5S
  • MW: 491.51900
  • Catalog: Endothelin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

[2S-(2alpha,4beta,5alpha)]-[tetrahydro-4-hydroxy-5-methylfurfuryl]trimethylammonium

Muscarine ((+)-Muscarine) is a toxin that can stimulate the parasympathetic nervous system. Muscarine is an agonist of muscarinic acetylcholine receptor (mAChR)[1][2].

  • CAS Number: 300-54-9
  • MF: C9H20NO2
  • MW: 174.26100
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MSX-127

MSX-127 is a CXCR4 antagonist. MSX-127 inhibits cancer metastasis[1].

  • CAS Number: 6616-56-4
  • MF: C16H24N2O4
  • MW: 308.37300
  • Catalog: CXCR
  • Density: 1.278g/cm3
  • Boiling Point: 486.7ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 248.2ºC

cis-(Z)-Flupentixol dihydrochloride

cis-(Z)-Flupentixol dihydrochloride is a potent and selective DA D1/D2 receptor antagonist, with Ki values of 0.38 nM and 7 nM for D2 receptor and 5-HT2A, respectively[1][2].

  • CAS Number: 51529-01-2
  • MF: C23H27Cl2F3N2OS
  • MW: 507.440
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: 554.7ºC at 760 mmHg
  • Melting Point: 194-202ºC
  • Flash Point: 289.3ºC

5-HT6/5-HT2A receptor ligand-1

5-HT6/5-HT2A receptor ligand-1 (compound 33) is a dual 5-HT6/5-HT2A receptor antagonist, with a Ki of 2 nM and 11 nM, respectively. 5-HT6/5-HT2A receptor ligand-1 has the potential for neurological and psychiatric disorders research[1].

  • CAS Number: 2411088-07-6
  • MF: C21H19FN2O2
  • MW: 350.39
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Amezinium methylsulfate

Amezinium metilsulfate has multiple mechanisms, including stimulation of alpha and beta-1 receptors and inhibition ofnoradrenaline and tyramine uptake. Target: alpha and beta-1 receptorsAmezinium metilsulfate is a sympathomimetic drug used for the treatment of low blood pressure. Cardiovascular effects of the new sympathomimetic Amezinium metilsulphate are investigated in 25 patients compared with a control group (n = 25). During spinal/epidural anaesthesia 5 mg amezinium is given i.v. if blood pressure dropped greater than 20 mmHg. from starting-point. A significant recovery of blood pressure (epidural anaesthesia: syst 21%, diast 9%; spinal anaesthesia: syst 13%, diast 6.6%) and a decrease in heart rate (6.8% resp. 4,5%) are thought due to peripheral vasoconstriction. Amezinium proves a stimulating drug for alpha- and beta 1-receptors by stabilising the systemic blood pressure in spinal/epidural anaesthesia.

  • CAS Number: 30578-37-1
  • MF: C12H15N3O5S
  • MW: 313.33000
  • Catalog: Adrenergic Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ligustroflavone

Ligustroflavone, extracted from Ligustrum lucidum, is a potential candidate as calcium-sensing receptor (CaSR) antagonist. Ligustroflavone exhibits protective effects against diabetic osteoporosis in mice[1].

  • CAS Number: 260413-62-5
  • MF: C33H40O18
  • MW: 724.66
  • Catalog: CaSR
  • Density: 1.7±0.1 g/cm3
  • Boiling Point: 1028.5±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 325.2±27.8 °C

(S)-(-)-Stepholidine

L-Stepholidine (Stepholidine), an alkaloid extract of the Chinese herb Stephania intermedia, is the first compound known to exhibit mixed dopamine D1 receptor agonist/D2 antagonist properties. L-Stepholidine (Stepholidine) has neuroprotective effect and inhibits heroin-induced reinstatement. L-Stepholidine (Stepholidine) is a potential medication for the treatment of opiate addiction[1][2][3].

  • CAS Number: 16562-13-3
  • MF: C19H21NO4
  • MW: 327.374
  • Catalog: Dopamine Receptor
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 524.0±50.0 °C at 760 mmHg
  • Melting Point: 120-122ºC
  • Flash Point: 270.7±30.1 °C

MRS2279

MRS2279 is a selective and high affinity P2Y1 receptor antagonist, with a Ki of 2.5 nM and an IC50 of 51.6 nM. MRS2279 competitively inhibits ADP-promoted platelet aggregation with an apparent affnity (pKB=8.05)[1][2].

  • CAS Number: 367909-40-8
  • MF: C13H18ClN5O8P2
  • MW: 469.71100
  • Catalog: P2Y Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GSK256073

GSK256073 is a potent, selective and orally active GPR109A agonist and a long-lasting and non-flushing HCA2 full agonist with a pEC50 of 7.5 (human HCA2). GSK256073 acutely improves glucose homeostasis via inhibition of lipolysis and has the potential for the study of type 2 diabetes mellitus (T2DM)and dyslipidemia[1][2]. GPR109A: G-protein coupled receptor 109A; HCA2: hydroxy-carboxylic acid receptor 2

  • CAS Number: 862892-90-8
  • MF: C10H13ClN4O2
  • MW: 256.68900
  • Catalog: GPR109A
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

N-Desethyloxybutynin hydrochloride

N-Desethyloxybutynin hydrochloride is an active metabolite of Oxybutynin. N-Desethyloxybutynin hydrochloride binds to mAChRs in isolated? human bladder and human parotid gland with pKi values of 8.2 and 8.7, respectively[1].

  • CAS Number: 81039-77-2
  • MF: C20H28ClNO3
  • MW: 365.89400
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 136-138ºC
  • Flash Point: N/A

(R,S)-MCPG

(RS)-MCPG is a non-selective group I/group II metabotropic glutamate receptor antagonist.

  • CAS Number: 146669-29-6
  • MF: C10H11NO4
  • MW: 209.19900
  • Catalog: mGluR
  • Density: 1.39g/cm3
  • Boiling Point: 230 °C17 mm Hg(lit.)
  • Melting Point: 95-98 °C(lit.)
  • Flash Point: 221-223°C/10mm

SB-209670

SB-209670 is an extremely potent and highly specific non-peptide, subnanomolar endothelin (ET) receptor antagonist. SB 209670 selectively inhibits binding of 125I-labeled ET-1 to cloned human ET receptor subtypes ETA and ETB (Ki=0.2 and 18 nM, respectively). SB 209670 produces a dose-dependent reduction in blood pressure in hypertensive rats, protects from ischemia-induced neuronal degeneration in a gerbil stroke model, and attenuates neointima formation following rat carotid artery balloon angioplasty[1].

  • CAS Number: 157659-79-5
  • MF: C29H28O9
  • MW: 520.53
  • Catalog: Endothelin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GPR84 antagonist 8

GPR84 antagonist 8 is a selective GPR84 antagonist.

  • CAS Number: 1445846-30-9
  • MF: C23H23N3O5
  • MW: 421.45
  • Catalog: GPR84
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GGTI-286

GGTI-286, a potent and cell-permeable GGTase I inhibitor, is 25-fold more potent (IC50=2 μM) than the corresponding methyl ester of FTI-276 (HY-15873A). GGTI-286 selectively inhibits geranylgeranylation of Rap1A over farnesylation of H-Ras in NIH3T3 cells (IC50s =2 and >30 μM, respectively). GGTI-286 also potently inhibits oncogenic K-Ras4B stimulation with an IC50 of 1 μM[1].

  • CAS Number: 171744-11-9
  • MF: C23H31N3O3S
  • MW: 429.58
  • Catalog: Ras
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 626.9±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 332.9±31.5 °C

DL-AP3

DL-AP3 is a competitive mGluR1 and mGluR5 antagonist. DL-AP3 is also an inhibitor of phosphoserine phosphatase. DL-AP3 has neuroprotective effect[1][2][3].

  • CAS Number: 5652-28-8
  • MF: C3H8NO5P
  • MW: 169.073
  • Catalog: mGluR
  • Density: 1.8±0.1 g/cm3
  • Boiling Point: 481.6±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 245.1±31.5 °C

Nocistatin

Nocistatin, a neuropeptide, is an endogenous ligand for the orphan opioid receptor-like receptor. Nocistatin is also a functional antagonist of neuropeptide nociceptin or orphanin FQ (Noc/OFQ). Nocistatin inhibits 5-HT release via a Gi/o proteinmediated pathway. Nocistatin blocks Nociceptin (Nociceptin)-induced allodynia and hyperalgesia[1][2].

  • CAS Number: 207392-60-7
  • MF: C32H56N10O12
  • MW: 772.85
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tropicamide-d3

Tropicamide-d3 is the deuterium labeled Tropicamide[1]. Tropicamide (Ro 1-7683) is a selective M4 muscarinic acetylcholine receptor antagonist. Tropicamide produces short acting mydriasis (dilation of the pupil) and cycloplegia when applied as eye drops[2][3].

  • CAS Number: 2673270-13-6
  • MF: C17H17D3N2O2
  • MW: 287.37
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Felcisetrag

Felcisetrag (TD-8954) is an orally active, potent and selective 5-HT4 receptor agonist with gastrointestinal prokinetic properties. Felcisetrag has high affinity (pKi =9.4) for human 5-HT4(c) receptors.

  • CAS Number: 916075-84-8
  • MF: C25H37N5O3
  • MW: 455.59
  • Catalog: 5-HT Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 691.6±25.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 372.0±23.2 °C

GT 2016

GT-2016 is a potent, selective, and brain penetrant histamine H3 receptor antagonist with a Ki of 43.8 nM. GT-2016 displays selectivity against H1 and H2 receptors, and has non-active against histamine methyltransferase[1].

  • CAS Number: 152241-24-2
  • MF: C19H31N3O
  • MW: 317.46900
  • Catalog: Histamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A