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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RP101075

RP101075, an active metabolite of Ozanimod, is a potent, orally active S1PR (sphingosine-1-phosphate receptor 1) agonist, with an EC50 of 0.27 nM. RP101075 displays >100-fold selectivity over S1PR5 (EC50=5.9 nM) and >10000-fold over S1PR 2, 3, and 4. RP101075 displays superior cardiovascular safety profile[1].

  • CAS Number: 1306760-73-5
  • MF: C21H20N4O2
  • MW: 360.4091
  • Catalog: LPL Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

C 021 dihydrochloride

C-021 dihydrochloride is a potent and orally bioavailable CCR4 antagonist with IC50 of 0.14 uM and 0.039 uM for inhibition of chemotaxis in human and mouse, respectively.

  • CAS Number: 1784252-84-1
  • MF: C27H41N5O2.2HCl
  • MW: 540.569
  • Catalog: CCR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Fesoterodine-d7 fumarate

Fesoterodine-d7 (fumarate) is the deuterium labeled Fesoterodine fumarate[1]. Fesoterodine Fumarate is an orally active, nonsubtype selective, competitive muscarinic receptor (mAChR) antagonist with pKi values of 8.0, 7.7, 7.4, 7.3, 7.5 for M1, M2, M3, M4, M5 receptors, respectively. Fesoterodine Fumarate is used for the overactive bladder (OAB)[2][3].

  • CAS Number: 2747918-94-9
  • MF: C30H34D7NO7
  • MW: 534.69
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Gramine

Gramine (Donaxine) is a natural alkaloid isolated from giant reed[2], acts as an active adiponectin receptor (AdipoR) agonist, with IC50s of 3.2 and 4.2 µM for AdipoR2 and AdipoR1, respectively[1]. Gramine is also a human and mouse β2-Adrenergic receptor (β2-AR) agonist[2]. Gramine (Donaxine) has anti-tumor, anti-viral and anti-inflammatory properties[1].

  • CAS Number: 87-52-5
  • MF: C11H14N2
  • MW: 174.242
  • Catalog: Autophagy
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 293.9±15.0 °C at 760 mmHg
  • Melting Point: 132-134 °C(lit.)
  • Flash Point: 131.5±20.4 °C

L-748,337

L748337 is a potent β3-adrenergic receptor antagonist and displays selectivity over β1 and β2 receptors. The Ki values of L748337 for β3-, β2- and β1-adrenoceptors are 4.0 nM, 204 nM and 390 nM, respectively[1]. L748337 couples predominantly to Gi to activate MAPK signaling and increases phosphorylation of Erk1/2 with pEC50 value of 11.6[2]. L748337 can be used for the research of cancer, nonalcoholic fatty liver disease (NAFLD), and cardiovascular related diseases[1][2][3].

  • CAS Number: 244192-94-7
  • MF: C26H31N3O5S
  • MW: 497.60600
  • Catalog: Adrenergic Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BI-0474

BI-0474 is a potent KRASG12C inhibitor with an IC50 value of 7.0 nM for the GDP-KRAS::SOS1 protein-protein interaction. BI-0474 exhibits good anti-proliferative activity against NCI-H358 cells carrying the G12C mutation. BI-0474 also shows good anti-tumour activity in non-small cell lung cancer xenograft models[1].

  • CAS Number: 2750570-55-7
  • MF: C30H37N9O2S
  • MW: 587.74
  • Catalog: Ras
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

mGluR3 modulator-1

mGluR3 modulator-1 (compound 3) is a mGluR3 modulator, with an EC50 of 1-10 μM in HEK293T-mGluR-Gqi5 Calcium Mobilization Assay[1].

  • CAS Number: 374548-18-2
  • MF: C16H21N3O
  • MW: 271.36
  • Catalog: mGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

6-(6-(4-hydroxypiperidinyl)hexyloxy)-3-methylflavone HCl

Sigma-LIGAND-1 hydrochloride is a selective sigma receptor ligand with an IC50s of 16 nM, 19 nM at the DTG site and the PPP site, respectively. Sigma-LIGAND-1 hydrochloride has a Ki of 4000 nM at the dopamine D2 receptor[1].

  • CAS Number: 139652-86-1
  • MF: C27H34ClNO4
  • MW: 472.01600
  • Catalog: Sigma Receptor
  • Density: N/A
  • Boiling Point: 615.5ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 326.1ºC

2-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-6,7-dimethoxy-quinolin-4-amine

Abanoquil (U-K52046), an potent and selective α-1 adrenoceptor antagonist, is an anti-arrhythmic agent. Abanoquil can be used for erectile dysfunction research[1][2].

  • CAS Number: 90402-40-7
  • MF: C22H25N3O4
  • MW: 395.45200
  • Catalog: Adrenergic Receptor
  • Density: 1.246g/cm3
  • Boiling Point: 630.3ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 335ºC

K-Ras G12C-IN-2

K-Ras G12C-IN-2 is a novel and irreversible inhibitor of G12C mutant K-Ras protein.

  • CAS Number: 1629267-75-9
  • MF: C21H27ClN4O3
  • MW: 418.917
  • Catalog: Ras
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 675.7±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 362.4±31.5 °C

RM-493

Setmelanotide acetate (RM-493 acetate) is a selective melanocortin 4 receptor (MC4R) agonist with EC50s of 0.27 nM and 0.28 nM for human and rat MC4R, respectively[1].

  • CAS Number: 1504602-49-6
  • MF: C49H68N18O9S2.xC2H4O2
  • MW:
  • Catalog: Endocrinology
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Saikogenin D

Saikogenin D is isolated from Bupleurum chinense, has anti-inflammatory effects. Saikogenin D activates epoxygenases that converts arachidonic acid to epoxyeicosanoids and dihydroxyeicosatrienoic acids, and the metabolites secondarily inhibit prostaglandin E2 (PGE2) production. Saikogenin D results in an elevation of [Ca2+]i due to Ca2+ release from intracellular stores[1][2].

  • CAS Number: 5573-16-0
  • MF: C30H48O4
  • MW: 472.700
  • Catalog: Prostaglandin Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 607.4±55.0 °C at 760 mmHg
  • Melting Point: 261-266 °C
  • Flash Point: 252.4±26.1 °C

Neuropeptide Y5 receptor ligand-1

Neuropeptide Y5 receptor ligand-1 (compound 54), a carbazole derivative, is a potent neuropeptide Y5 (NPY-5) receptor antagonist[1].

  • CAS Number: 322723-35-3
  • MF: C19H17N3O2
  • MW: 319.36
  • Catalog: Neuropeptide Y Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

mAChR antagonist 1

mAChR antagonist 1 (compound 4a) is a mAChR antagonist with Ki values of 255 nM, 121 nM, 158 nM, and 255 nM for M1, M3, M4, and M5 subtype, respectively[1].

  • CAS Number: 101491-79-6
  • MF: C19H22N2O2
  • MW: 310.39000
  • Catalog: mAChR
  • Density: 1.18g/cm3
  • Boiling Point: 437ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 218.1ºC

PW0464

PW0464, a nanomolar potent complete G protein biased ligand, is a noncatechol D1R agonist, with an EC50 of 5.8 nM (Gs-cAMP)[1].

  • CAS Number: 1643462-93-4
  • MF: C19H17F2N3O4
  • MW: 389.35
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

VUF8430 dihydrobromide

VUF 8430 (dihydrobromide) is a potent and selective histamine H4 receptor agonist with a Ki of 31.6 nM and an EC50 of 50 nM[1].

  • CAS Number: 100130-32-3
  • MF: C4H13Br2N5S
  • MW: 323.05300
  • Catalog: Histamine Receptor
  • Density: N/A
  • Boiling Point: 348.8ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 164.8ºC

PD 168077 maleate

PD-168077 maleate is a selective dopamine D4 receptor agonist, with a Ki of 9 nM.

  • CAS Number: 630117-19-0
  • MF: C24H26N4O5
  • MW: 450.487
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CP-66948

CP-66948 is a histamine H2-receptor antagonist with gastric antisecretory activity and mucosal protective properties.

  • CAS Number: 101189-47-3
  • MF: C13H20N6S
  • MW: 292.40300
  • Catalog: Histamine Receptor
  • Density: 1.34g/cm3
  • Boiling Point: 561.6ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 293.4ºC

SDF-1α (human) trifluoroacetate salt

SDF-1α (human) is a mononuclear cells chemoattractant that can bind to CXCR4. SDF-1α plays a central role in stem cell homing, retention, survival, proliferation, cardiomyocyte repair, angiogenesis and ventricular remodelling following myocardial infarction. SDF-1α (human) can be used in cardiovascular disease research[1][2].

  • CAS Number: 1268129-65-2
  • MF: C356H578N106O93S4
  • MW: 7959.43
  • Catalog: CXCR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cetirizine

Cetirizine, a second-generation antihistamine, is a major metabolite of hydroxyzine, and a racemic selective H1 receptor inverse agonist used in the treatment of allergies, hay fever, angioedema, and urticaria. IC50 value:Target: Histamine H1 receptorCetirizine crosses the blood-brain barrier only slightly, reducing the sedative side-effect common with older antihistamines. It has also been shown to inhibit eosinophil chemotaxis and LTB4 release. At a dosage of 20 mg, Boone et al. found that it inhibited the expression of VCAM-1 in patients with atopic dermatitis. The levorotary enantiomer of cetirizine, known as levocetirizine, is the more active form. From Wikipedia.

  • CAS Number: 83881-51-0
  • MF: C21H25ClN2O3
  • MW: 388.888
  • Catalog: Histamine Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 542.1±45.0 °C at 760 mmHg
  • Melting Point: 110-115°C
  • Flash Point: 281.6±28.7 °C

VU0424238

VU0424238 is a novel and selective mGlu5 antagonist with an IC50 value of 11 nM (rat) and an IC50 value of 14 nM (human). VU0424238 has an acceptable CNS penetration[1].

  • CAS Number: 1396337-04-4
  • MF: C16H12FN5O2
  • MW: 325.30
  • Catalog: mGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Seltorexant hydrochloride

Seltorexant hydrochloride (JNJ-42847922 hydrochloride) is an orally active, high-affinity, and selective OX2R antagonist (pKi values of 8.0 and 8.1 for human and rat OX2R). Seltorexant hydrochloride crosses the blood-brain barrier and quickly occupies OX2R binding sites in the rat brain[1].

  • CAS Number: 1293284-49-7
  • MF: C21H23ClFN7O
  • MW: 443.91
  • Catalog: Orexin Receptor (OX Receptor)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Antazoline

Antazoline is an H1 receptor antagonist that affects the activity of the central nervous system, has a potent antiarrhythmic effect[1][2][3].

  • CAS Number: 91-75-8
  • MF: C17H19N3
  • MW: 265.353
  • Catalog: Histamine Receptor
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 475.5±38.0 °C at 760 mmHg
  • Melting Point: 159ºC
  • Flash Point: 241.4±26.8 °C

ly 272015 hydrochloride

LY-272015 hydrochloride is an orally active, specific 5-HT2B receptor antagonist. LY-272015 hydrochloride completely inhibits the phosphorylation of ERK2 induced by 5-HT or BW723C86. LY-272015 hydrochloride is antihypertensive in Deoxycorticosterone Acetate (DOCA)-salt-hypertensive rats[1][2].

  • CAS Number: 172895-15-7
  • MF: C21H25ClN2O2
  • MW: 372.88800
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Vabicaserin hydrochloride (SCA 136)

Vabicaserin hydrochloride is a 5-hydroxytryptamine 2C (5-HT2C) receptor-selective agonist with an EC50 of 8 nM.

  • CAS Number: 887258-94-8
  • MF: C15H21ClN2
  • MW: 264.79
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(Z)-Thiothixene

(Z)-Thiothixene is an antagonist of serotonergic receptor extracted from patent US 20150141345 A1.

  • CAS Number: 3313-26-6
  • MF: C23H29N3O2S2
  • MW: 443.62500
  • Catalog: 5-HT Receptor
  • Density: 1.269 g/cm3
  • Boiling Point: 599ºC at 760 mmHg
  • Melting Point: 114-118ºC
  • Flash Point: 316.1ºC

GPR120 Agonist 2

GPR120 Agonist 2 is a GPR120 agonist extracted from patent US 20110313003 A1, example 209.

  • CAS Number: 1234844-11-1
  • MF: C22H25ClO4
  • MW: 388.88
  • Catalog: GPR120
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Sotalol D6 hydrochloride

Sotalol D6 hydrochloride is a deuterium labeled Sotalol hydrochloride. Sotalol hydrochloride is a non-selective competitive β-adrenergic receptor antagonist that also exhibits Class III antiarrhythmic properties by its inhibition of potassium channels[1][2].

  • CAS Number: 1246820-85-8
  • MF: C12H15D6ClN2O3S
  • MW: 314.862
  • Catalog: Adrenergic Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

[Leu31,Pro34]-Neuropeptide Y (porcine)

[Leu31,Pro34]- Neuropeptide Y (porcine), a Neuropeptide Y (NPY) analog, is a selective NPY Y1 receptor agonist. [Leu31,Pro34]- Neuropeptide Y (porcine) exhibits anxiolytic effects[1][2].

  • CAS Number: 125580-28-1
  • MF: C190H286N54O56
  • MW: 4222.63
  • Catalog: Neuropeptide Y Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Syk Inhibitor II dihydrochloride dihydrate

Syk Inhibitor II dihydrochloride dihydrate is a potent, high selective and ATP-competitive Syk inhibitor with an IC50 of 41 nM. Syk Inhibitor II dihydrochloride dihydrate inhibits 5-HT release from RBL-cells with an IC50 of 460 nM. Syk Inhibitor II dihydrochloride dihydrate shows less potent against other kinases and has anti-allergic effect[1].

  • CAS Number: 1965323-05-0
  • MF: C14H21Cl2F3N6O3
  • MW: 449.26
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A