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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AM966

AM966 is a high affinity, selective, oral LPA1-antagonist, inhibits LPA-stimulated intracellular calcium release (IC50=17 nM).

  • CAS Number: 1228690-19-4
  • MF: C27H23ClN2O5
  • MW: 490.93500
  • Catalog: LPL Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Nebivolol

(Rac)-Nebivolol ((Rac)-R 065824) is a racemic isomer of Nebivolol. Nebivolol is a selective β1-adrenergic receptor antagonist with an IC50 value of 0.8 nM. Nebivolol can prevent up-regulation of Nox2/NADPH oxidase and lipoperoxidation in the early stages of ethanol-induced cardiac toxicity. Vasodilatory activity[1][2].

  • CAS Number: 99200-09-6
  • MF: C22H25F2NO4
  • MW: 405.43500
  • Catalog: Adrenergic Receptor
  • Density: 1.309 g/cm3
  • Boiling Point: 600.5ºC at 760 mmHg
  • Melting Point: 155-156°C(lit.)
  • Flash Point: 316.9ºC

6-Alpha Naloxol

6-Alpha Naloxol(Alpha-Naloxol) is an opioid antagonist closely related to naloxone; a human metabolite of naloxone.IC50 value:Target: opioid antagonistWhen responding over the entire 30 min operant session was examined, naloxone was only 5-fold more potent than 6-alpha-naloxol in suppressing operant responding under Morphine Na ve conditions, but this increased to a 65-fold potency difference after Single or Repeat Morphine pretreatment. Examination of the relative potency of these antagonists in the Early Phase of operant testing (5-15 min post-antagonist) revealed an even greater 100-fold potency difference between naloxone and 6-alpha-naloxol, but in the Late Phase of testing (25-35 min post-antagonist), this had declined to a 9-fold potency difference, comparable to the relative potency of naloxone to 6-alpha-naloxol under Morphine-Na ve conditions.

  • CAS Number: 20410-95-1
  • MF: C19H23NO4
  • MW: 329.39000
  • Catalog: Opioid Receptor
  • Density: 1.43g/cm3
  • Boiling Point: 532.5ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 275.8ºC

(S)-Carvedilol-d4

(S)-Carvedilol-d4 is deuterium labeled (S)-Carvedilol. (S)-Carvedilol, the S-enantiomer of Carvedilol, is a non-selective β/α-1 blocker. (S)-Carvedilol exerts protection against the vascular or cardiac toxicity of Doxorubicin (DOX)[1].

  • CAS Number: 2747915-23-5
  • MF: C24H22D4N2O4
  • MW: 410.50
  • Catalog: Adrenergic Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MPPG

MPPG is a potent and selective L-AP4-sensitive receptor antagonist with an kD value of 9.2 μM, being tested on the neonatal rat spinal cord[1].

  • CAS Number: 169209-65-8
  • MF: C9H12NO5P
  • MW: 245.16900
  • Catalog: mGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

pasireotide

Pasireotide(SOM 230) is a stable cyclohexapeptide somatostatin mimic that exhibits unique high-affinity binding to human somatostatin receptors (subtypes sst1/2/3/4/5, pKi=8.2/9.0/9.1/<7.0/9.9 respectively).IC50 value: 8.2/9.0/9.1/<7.0/9.9(pKi, sst1/2/3/4/5) [1]in vitro: SOM230 showed a lower potency of GH release inhibition (IC(50), 0.5 nM), compared with OCT (IC(50), 0.02 nM) and SRIF-14 (IC(50), 0.02 nM). A positive correlation was found between sst(2) but not sst(5) mRNA levels in the adenoma cells and the inhibitory potency of OCT on GH release in vivo and in vitro, and the effects of SOM230 and SRIF-14 in vitro [2]. In cultures of human fetal pituitary cells, SOM230 inhibited GH secretion by 42 +/- 9% (P = 0.002) but had no effect on TSH release. SOM230 inhibited GH release from GH-secreting adenoma cultures by 34 +/- 8% (P = 0.002), PRL by 35 +/- 4% from PRL-secreting adenomas (P = 0.01), and alpha-subunit secretion from nonfunctioning pituitary adenomas by 46 +/- 18% (P = 0.34) [3].in vivo: On day 7, there was a decrease in serum insulin levels from 1.06 ± 0.28 μg/L to 0.37 ± 0.17 μg/L (P = .0128) and a significant increase in serum glucose from 4.2 ± 0.45 mmol/L to 7.12 ± 1.06 mmol/L (P = .0075) in the treatment group but no change in the control group [4]. In wild-type mice, both octreotide and pasireotide significantly attenuated knee joint swelling and histopathologic manifestations of arthritis to an extent comparable to that of dexamethasone. In SSTR2(-/-) mice, the antiinflammatory effects of both octreotide and pasireotide were completely abrogated [5].

  • CAS Number: 396091-73-9
  • MF: C58H66N10O9
  • MW: 1047.206
  • Catalog: Somatostatin Receptor
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 1351.4±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 771.1±34.3 °C

Sipagladenant

Sipagladenant (Compound I) is an orally active adenosine receptor A2A inverse agonist[1]. Sipagladenant can be used in frontal lobe dysfunction research[2].

  • CAS Number: 858979-50-7
  • MF: C20H19N3O4S
  • MW: 397.45
  • Catalog: Adenosine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Levocabastine hydrochloride

Levocabastine (R 50547) hydrochloride is a long acting, highly potent and selective histamine H1-receptor antagonist with anti-allergic activity. Levocabastine hydrochloride is also a selective, high affinity neurotensin receptor subtype 2 (NTR2) antagonist, with a Ki of 17 nM for mNTR2[1][2].

  • CAS Number: 79547-78-7
  • MF: C26H30ClFN2O2
  • MW: 456.98000
  • Catalog: Histamine Receptor
  • Density: N/A
  • Boiling Point: 611ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 323.3ºC

W146 TFA

W146 TFA is a selective antagonist of sphingosine-1-phosphate receptor 1 (S1PR1) with an EC50 value of 398 nM.

  • CAS Number: 909725-62-8
  • MF: C18H28F3N2O6P
  • MW: 456.4
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GSK598809

GSK598809 is a potent and selective dopamine D3 Receptor (DRD3) antagonist, with a pKi of 8.9.

  • CAS Number: 863680-45-9
  • MF: C22H23F4N5OS
  • MW: 481.51
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Relugolix

Relugolix is a novel, non-peptide, orally active gonadotropin-releasing hormone (GnRH) antagonist with IC50 of 0.33 nM in the presence of 40% fetal bovine serum, TAK-385 possesses higher affinity and potent antagonistic activity compared with TAK-013.target: GnRH [1]IC50: 0.33 nM [1]In vivo: In female knock-in mice, twice-daily oral administration of TAK-385 (100mg/kg) induces constant diestrous phases within the first week, decreases the uterus weight to ovariectomized levels and downregulated GnRH receptor mRNA in the pituitary after 4 weeks.[2]

  • CAS Number: 737789-87-6
  • MF: C29H27F2N7O5S
  • MW: 623.63
  • Catalog: GNRH Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Rapacuronium Bromide

Rapacuronium bromide is an allosteric modulator of muscarinic acetylcholine receptor (mAChR).

  • CAS Number: 156137-99-4
  • MF: C37H61BrN2O4
  • MW: 677.79500
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MRS 5698

MRS5698 is a selective Gi protein-coupled A3 adenosine receptor (A3AR) agonist, with Kis of approximately 3 nM for human and mouse A3AR, respectively. MRS5698 can be used for the research of pain and psoriasis[1][2].

  • CAS Number: 1377273-00-1
  • MF: C28H23ClF2N6O3
  • MW: 564.97000
  • Catalog: Adenosine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ONO-0300302

ONO-0300302 (ONO0300302) is a novel potent, slow tight binding LPA1 receptor antagonist with IC50 of 86 nM, Kd of 0.34 nM; shows excellent in vivo efficacy, represents a best research tool available to LPA-related diseases.

  • CAS Number: 856689-51-5
  • MF: C29H35NO5
  • MW: 477.601
  • Catalog: LPL Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

VPC 23019

VPC23019, an aryl amide-containing Sphingosine 1-phosphate (S1P) analog, is a competitive antagonist at the S1P1 and S1P3 receptors (pKi= 7.86 and 5.93, respectively) and a agonist at the S1P4 and S1P5 receptors (pEC50= 6.58 and 7.07, respectively)[1].

  • CAS Number: 449173-19-7
  • MF: C17H29N2O5P
  • MW: 372.39600
  • Catalog: LPL Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

L162389

L162389 is a potent antagonist of angiotensin AT1 receptor with Ki of 28 nM.

  • CAS Number: 169281-53-2
  • MF: C31H38N4O4S
  • MW: 562.723
  • Catalog: Angiotensin Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AM095

AM095 is a selective LPA1 receptor antagonist. The IC50 for AM095 antagonism of LPA-induced calcium flux of human or mouse LPA1-transfected CHO cells is 0.025 and 0.023 μM, respectively.

  • CAS Number: 1345614-59-6
  • MF: C27H23N2NaO5
  • MW: 478.47200
  • Catalog: LPL Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(S)-3,5-DHPG

(S)-3,5-DHPG is a weak, but selective group I metabotropic glutamate receptors (mGluRs) agonist with Ki values of 0.9 µM and 3.9 µM for mGluR1a and mGluR5a, respectively[1]. (S)-3,5-DHPG exhibits anxiolytic activity in rats subjected to hypoxia[2].

  • CAS Number: 162870-29-3
  • MF: C8H9NO4
  • MW: 183.161
  • Catalog: mGluR
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 448.8±33.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 225.2±25.4 °C

CI 988

CI-988 (PD134308) is a potent, selective and orally active CCK2R (cholecystokinin 2 receptor) antagonist with an IC50 of 1.7 nM for mouse cortex CCK2. CI-988 shows >1600-fold selectivity for CCK2 over CCK1 receptor. CI-988 has anxiolytic and anti-tumor effects[1][2][3].

  • CAS Number: 130332-27-3
  • MF: C35H42N4O6
  • MW: 614.73100
  • Catalog: Cholecystokinin Receptor
  • Density: 1.32g/cm3
  • Boiling Point: 949.6ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: N/A

PF 04628935

PF-04628935 (compound 10n) is a potent ghrelin receptor inverse agonist, with an IC50 of 4.6 nM. PF-04628935 exhibits oral bioavailability of 43% in rats and shows reasonable penetration into the brain. PF-04628935 can be used for stress and anxiety research[1][2].

  • CAS Number: 1383719-97-8
  • MF: C24H26ClN7OS
  • MW: 496.03
  • Catalog: GHSR
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

[Orn8]-Urotensin II acetate

[Orn8]-Urotensin II acetate is a Urotensin receptor ligand and a partial agonist at Urotensin receptors.

  • CAS Number: 479065-85-5
  • MF: C65H87N13O20S2
  • MW: 1434.59
  • Catalog: Urotensin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

WAY-181187 hydrochloride

WAY-181187 (SAX-187) hydrochloride 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]. WAY-181187 hydrochloride mediates 5-HT6 receptor-dependent signal pathways, such as cAMP, Fyn and ERK1/2 kinase, as specific agonist[2].

  • CAS Number: 554403-08-6
  • MF: C15H14Cl2N4O2S2
  • MW: 417.33
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SB-649868

SB-649868 is a potent and selective orally active orexin (OX) 1 and OX2 receptor antagonist (pKi =9.4 and 9.5 at the OX1 and OX2 receptor, respectively).

  • CAS Number: 380899-24-1
  • MF: C26H24FN3O3S
  • MW: 477.55000
  • Catalog: Orexin Receptor (OX Receptor)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NVS-CRF38

NVS-CRF38 is a novel corticotropin-releasing factor receptor 1 (CRF1) antagonist with low water solubility.IC50 value: Target: CRF1 antagonist

  • CAS Number: 1207258-55-6
  • MF: C19H21N5O2
  • MW: 351.40200
  • Catalog: CRFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Endothelin Mordulator 1

Endothelin Mordulator 1 is a endothelin receptor modulator, used for the research of endothelin-mediated disorders.

  • CAS Number: 349453-49-2
  • MF: C20H21N3O5S2
  • MW: 447.53
  • Catalog: Endothelin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GR 73632

GR-73632 is a novel tachykinin neurokinin 1 (NK-1) receptor agonist[1]. GR-73632 acts directly on the peripheral terminals of primary sensory neurons through NK1 receptor which convey itch signals[2].

  • CAS Number: 133156-06-6
  • MF: C40H59N7O6S
  • MW: 766.00500
  • Catalog: Neurokinin Receptor
  • Density: 1.198g/cm3
  • Boiling Point: 1082.2ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 608.3ºC

Vapreotide acetate

Vapreotide acetate is a synthetic analog of somatostatin for the treatment of variceal bleeding; also exhibits antitumor activity.

  • CAS Number: 849479-74-9
  • MF: C57H70N12O9S2.xC2H4O2
  • MW: 1209.438
  • Catalog: Somatostatin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Urocortin III (human) trifluoroacetate salt

Urocortin III (human) is a corticotropin-releasing factor (CRF)-related peptide. Urocortin III (human) preferentially binds and activates CRF-R2 and has a discrete central nervous system and peripheral distribution. Urocortin III (human) selectively binds to type 2 CRF receptors with Ki values of 13.5, 21.7, and >100 nM for mCRF2β, rCRF2α, and hCRF1, respectively. Urocortin III (human) mediates somatostatin-dependent negative feedback control of Insulin (human) (HY-P0035) secretion[1][2].

  • CAS Number: 357952-09-1
  • MF: C185H307N53O50S2
  • MW:
  • Catalog: CRFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Setmelanotide

Setmelanotide (RM-493;BIM-22493;IRC-022493) is a melanocortin 4 receptor (MC4R) agonist with an EC50 of 0.27 nM for human MC4R.

  • CAS Number: 920014-72-8
  • MF: C49H68N18O9S2
  • MW: 1117.309
  • Catalog: Metabolic Disease
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NAEPA

NAEPA, a phosphate-mimetic derivative, is a lysophosphatidic acid (LPA) receptor agonist[1].

  • CAS Number: 24435-25-4
  • MF: C20H40NO5P
  • MW: 405.50900
  • Catalog: LPL Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 75.8-84.0ºC
  • Flash Point: N/A