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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(Deamino-Cys1,β-(3-pyridyl)-D-Ala2,Arg8)-Vasopressin trifluoroacetate salt

Desamino(D-3-(3′-pyridyl)-Ala2,Arg8)-Vasopressin, a synthetic analog of vasopressin (AVP), is a weak agonist at antidiuretic receptor. However, Desamino(D-3-(3′-pyridyl)-Ala2,Arg8)-Vasopressin is a potent agonist at pituitary corticotrope receptor[1].

  • CAS Number: 136105-89-0
  • MF: C45H63N15O11S2
  • MW: 1054.21000
  • Catalog: Vasopressin Receptor
  • Density: 1.56g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CP 376395 hydrochloride

CP 376395 hydrochloride is a potent, selective, and brain-penetrable Corticotropin releasing factor 1 (CRF1) receptor antagonist[1][2].

  • CAS Number: 1013933-37-3
  • MF: C21H31ClN2O
  • MW: 362.94
  • Catalog: CRFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Labetalol

Labetalol (AH5158) is an orally active selective α1- and non-selective β-adrenergic receptors competitive antagonist. Labetalol, an anti-hypertensive agent, can be used for the research of cardiovascular disease, such as hypertension in pregnancy[1][2][3].

  • CAS Number: 36894-69-6
  • MF: C19H24N2O3
  • MW: 328.405
  • Catalog: Adrenergic Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 552.7±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 288.1±30.1 °C

SQ-29548

SQ 29548, a high affinity radioligand, is a selective thromboxane-prostanoid (TP) receptor antagonist[1][2].

  • CAS Number: 98672-91-4
  • MF: C21H29N3O4
  • MW: 387.473
  • Catalog: Prostaglandin Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Fenmetozole Tosylate

Fenmetozole Tosylate is an antagonist of the actions of ethanol, also antagonizes α2-adrenergic receptor, and acts as an antidepressant drug.

  • CAS Number: 83474-08-2
  • MF: C17H18Cl2N2O4S
  • MW: 417.31
  • Catalog: Adrenergic Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

RTI-118

RTI-118 is a novel small-molecule neuropeptide S receptor (NPSR) antagonist. RTI-118 can relieve drug addiction including selectively decrease cocaine self-administration[1].

  • CAS Number: 847554-50-1
  • MF: C26H32N4O3
  • MW: 448.56
  • Catalog: Neuropeptide Y Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

A1AR antagonist 6

A1AR antagonist 6 (compound 15) is a potent and selective A1AR (A1 adenosine receptor) antagonist, with a pIC50 of 6.38 and a pKi of 7.13[1].

  • CAS Number: 329693-22-3
  • MF: C17H15N3O2
  • MW: 293.32
  • Catalog: Adenosine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PRECLAMOL HYDROCHLORIDE

Preclamol hydrochloride ((-)-3-PPP hydrochloride) is a selective dopamine autoreceptor agonist. Preclamol hydrochloride has the potential for the research of schizophrenia[1][2].

  • CAS Number: 88768-67-6
  • MF: C14H22ClNO
  • MW: 255.78
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: 342.2ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 158ºC

(±)-Befunolol

(±)-Befunolol is a β-adrenoceptor blocking agent.

  • CAS Number: 39552-01-7
  • MF: C16H21NO4
  • MW: 291.34200
  • Catalog: Adrenergic Receptor
  • Density: 1.1049 (rough estimate)
  • Boiling Point: 433.35°C (rough estimate)
  • Melting Point: 115°
  • Flash Point: N/A

VU 0650786

VU0650786 is a potent and selective CNS penetrant negative allosteric modulator of metabotropic glutamate receptor subtype 3 (mGlu3), with an IC50 of 392 nM. VU0650786 has antidepressant and anxiolytic activity in rodents[1].

  • CAS Number: 1809085-30-0
  • MF: C18H15ClFN5O2
  • MW: 387.80
  • Catalog: mGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Firazorexton hydrate

Firazorexton hydrate (TAK-994) is a potent, brain-penetrant, and orally active orexin type 2 receptor (OX2R) agonist (EC50: 19 nM). Firazorexton hydrate inhibits fragmentation of wakefulness and cataplexy-like episodes in mouse models of narcolepsy[1].

  • CAS Number: 2861934-86-1
  • MF: C22H25F3N2O4S.3/2H2O
  • MW: 497.53
  • Catalog: Orexin Receptor (OX Receptor)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Zendusortide

Zendusortide is a sortilin binding peptide[1].

  • CAS Number: 2098662-44-1
  • MF: C85H138N26O25
  • MW: 1924.16
  • Catalog: Neurotensin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Rotigotine

Rotigotine is a full agonist of dopamine receptor, a partial agonist of the 5-HT1A receptor, and an antagonist of the α2B-adrenergic receptor, with Kis of 0.71 nM, 4-15 nM, and 83 nM for the dopamine D3 receptor and D2, D5, D4 receptors, and dopamine D1 receptor.

  • CAS Number: 99755-59-6
  • MF: C19H25NOS
  • MW: 315.473
  • Catalog: 5-HT Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 470.1±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 238.1±28.7 °C

NNC 63-0532

NNC63-0532 is a novel non-peptide nociceptin receptor (ORL1) agonist, with EC50s of 305?nM. NNC63-0532 plays important roles in many disorders such as pain, drug addiction[1].

  • CAS Number: 250685-44-0
  • MF: C27H29N3O3
  • MW: 443.53700
  • Catalog: Opioid Receptor
  • Density: 1.28g/cm3
  • Boiling Point: 645.8ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 344.4ºC

Diphenidol (hydrochloride)

Diphenidol hydrochloride is a muscarinic antagonist employed as an antiemetic and as an antivertigo agent.

  • CAS Number: 3254-89-5
  • MF: C21H28ClNO
  • MW: 345.91
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: 473.3ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 233.5ºC

Muscarine tosylate

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

  • CAS Number: 82083-43-0
  • MF: C16H27NO5S
  • MW: 345.45
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JTP-117968

JTP-117968, a novel selective glucocorticoid receptor modulator (a non-steroidal SGRM, IC50 of 6.8 nM), exhibits improved transrepression/transactivation dissociation[1].

  • CAS Number: 2250132-99-9
  • MF: C31H31F3N2O2
  • MW: 520.59
  • Catalog: Glucocorticoid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

K-Ras-IN-2

K-Ras-IN-2 (Compound CHI-000-667) is a K-Ras antagonist, and can be used for tumor research[1].

  • CAS Number: 905794-70-9
  • MF: C21H16ClNO4S
  • MW: 413.87
  • Catalog: Ras
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Asimilobine

Asimilobine is an aporphine isoquinoline alkaloid isolated from plant species of Magnolia obobata Thun. Asimilobine is a dopamine biosynthesis inhibitor and a serotonergic receptor antagonist. Asimilobine shows an antimalarial and anti-cancer activity[1][2].

  • CAS Number: 6871-21-2
  • MF: C17H17NO2
  • MW: 267.322
  • Catalog: 5-HT Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 472.5±45.0 °C at 760 mmHg
  • Melting Point: 177-179℃ (acetone )
  • Flash Point: 239.6±28.7 °C

6-Chloromelatonin

6-Chloromelatonin is a potent melatonin receptor agonist with greater metabolic stability than melatonin. 6-Chloromelatonin compete for [3H]-melatonin and 2-[125I]-iodomelatonin binding to MT1 receptors (pKi=8.9 and 9.1, respectively). 6-Chloromelatonin compete for [3H]-melatonin binding to MT2 receptors (pKi=9.77)[1][2].

  • CAS Number: 63762-74-3
  • MF: C13H15ClN2O2
  • MW: 266.72300
  • Catalog: Melatonin Receptor
  • Density: 1.272g/cm3
  • Boiling Point: 536.7ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 278.4ºC

MSOP

MSOP is a selective group III metabotropic glutamate receptor antagonist with apparent KD of 51 μM for the L-AP4-sensitive presynaptic mGluR.

  • CAS Number: 66515-29-5
  • MF: C4H10NO6P
  • MW: 199.10
  • Catalog: mGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CCG-100602

CCG-100602 is a specific inhibitor of myocardin-related transcription factor A/serum response factor (MRTF-A/SRF) signaling. CCG-100602 specifically block MRTF-A nuclear localization and thus inhibit the fibrogenic transcription factor SRF[1][2].

  • CAS Number: 1207113-88-9
  • MF: C21H17ClF6N2O2
  • MW: 478.815
  • Catalog: Ras
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 563.8±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 294.8±30.1 °C

AIDA

UPF-523 (AIDA), a rigid (carboxyphenyl) glycine derivative, is a relatively potent and selective antagonist of group I metabotropic glutamate receptors (mGlu1a) with an IC50 of 214 μM. But UPF-523 has no effect on group II (mGlu2), group III (mGlu4) receptors or ionotropic glutamate receptors. UPF-523 has the potential for the research of the acute arthritis[1][2].

  • CAS Number: 168560-79-0
  • MF: C11H11NO4
  • MW: 221.20900
  • Catalog: mGluR
  • Density: 1.481 g/cm3
  • Boiling Point: 470.4ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 238.3ºC

4-Methylhistamine dihydrochloride

4-Methylhistamine (dihydrochloride) is the potent agonist of histamine 4 receptor (H4R). 4-Methylhistamine (dihydrochloride) has the potential for the research of immune-related diseases such as cancer and autoimmune disorders[1].

  • CAS Number: 36376-47-3
  • MF: C6H13Cl2N3
  • MW: 198.09400
  • Catalog: Histamine Receptor
  • Density: 1.1g/cm3
  • Boiling Point: 345ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 189.3ºC

thiethylperazine

Thiethylperazine, a phenothiazine derivate, is an orally active and potent dopamine D2-receptor and histamine H1-receptor antagonist. Thiethylperazine is also a selective ABCC1activator that reduces amyloid-β (Aβ) load in mice. Thiethylperazine has anti-emetic, antipsychotic and antimicrobial effects[1][2][3].

  • CAS Number: 1420-55-9
  • MF: C22H29N3S2
  • MW: 399.61600
  • Catalog: Bacterial
  • Density: 1.24g/cm3
  • Boiling Point: 559.8ºC at 760mmHg
  • Melting Point: 62-64°
  • Flash Point: 292.4ºC

BIBP3226trifluoroacetate

BIBP3226 TFA is a potent and selective neuropeptide Y Y1 (NPY Y1) and neuropeptide FF (NPFF) receptor antagonist, with Kis of 1.1, 79, and 108 nM for rNPY Y1, hNPFF2, and rNPFF, respectively. BIBP3226 TFA displays anxiogenic-like effect[1][2].

  • CAS Number: 1068148-47-9
  • MF: C29H32F3N5O5
  • MW: 587.59
  • Catalog: Neuropeptide Y Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

S-(-)-Alprenolol

(S)-Alprenolol is a potent and nonselective β-blocker[1].

  • CAS Number: 23846-71-1
  • MF: C15H23NO2
  • MW: 249.34900
  • Catalog: Adrenergic Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ML-224

ML224(NCGC00242364; ANTAG3) is a selective TSHR inverse agonist; inhibits TSH-stimulated cAMP production with an IC50 = 2.3 μM.IC50 value: 2.3 uM [1]Target: TSHR agonistin vitro: ANTAG3 was selective for TSHR inhibition; half-maximal inhibitory doses were 2.1 μM for TSHR and greater than 30 μM for LH and FSH receptors [2]. in vivo: In mice treated with TRH, ANTAG3 lowered serum free T4 by 44% and lowered mRNAs for sodium-iodide cotransporter and thyroperoxidase by 75% and 83%, respectively. In mice given M22, ANTAG3 lowered serum free T4 by 38% and lowered mRNAs for sodium-iodide cotransporter and thyroperoxidase by 73% and 40%, respectively [2].

  • CAS Number: 1338824-21-7
  • MF: C31H31N3O5
  • MW: 525.595
  • Catalog: TSH Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 752.3±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 408.8±32.9 °C

GSK1292263

GSK1292263 is a novel GPR119 receptor agonist used for the treatment of type 2 diabetes.IC50 value:Target: GPR119in vitro: GSK-1292263 is selected from 1538 compounds by using Hypo1, the Fit-Value and Estimate of GSK-1292263 that is aligned in Hypo1 are 8.8 and 7.7 (nM), respectively [1]. in vivo: GSK-1292263 administrated at a single dose of 3-30 mg/kg in the absence of nutrients correlates with increased levels of circulating gastrointestinal peptides, including glucagon-like peptide 1 (GLP-1), gastric inhibitory polypeptide (GIP), peptide YY (PYY) and glucagon in male Sprague-Dawley rats, the increase is enhanced following administration of glucose in the oral glucose tolerance test (OGTT). GSK-129226 significant increases in the peak insulin response and insulin AUC(0-15 min) of 30-60% compared with values in the vehicle control cohort in the intravenous glucose tolerance test in rats, this insulin upregulation correlated with a significant increase in the glucose disposal rate. GSK-1292263 is associated with a statistically significant increase in insulin immunoreactivity in pancreatic sections in a 6-week study performed in Zucker diabetic fatty rats, compared with insulin immunoreactivity in samples obtained from rats receiving vehicle control. GSK-1292263 administrated at dose of 10 or 30 mg/kg or vehicle control at 2 hours prior to insulin infusion in hyperinsulinemic-euglycemic clamps stimulates glucagon secretion without increasing blood glucose levels Sprague-Dawley rats [2].

  • CAS Number: 1032823-75-8
  • MF: C23H28N4O4S
  • MW: 456.558
  • Catalog: GPR119
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 655.1±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 350.0±34.3 °C

KRAS G12D inhibitor 9

KRAS G12D inhibitor 9 is a potent inhibitor of KRAS G12D. The Ras family of proteins is an important intracellular signaling molecule that plays an important role in growth and development. KRAS G12D inhibitor 9 has the potential for the research of KRAS G12D-mediated cancer (extracted from patent WO2021108683A1, compound 20)[1].

  • CAS Number: 2648551-39-5
  • MF: C33H43N7O2
  • MW: 569.74
  • Catalog: Ras
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A