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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4F 4PP oxalate

4F 4PP (oxalate) is a selective 5-HT2A antagonist with almost as high affinity (Ki= 5.3 nM) as ketanserin but with a much lower affinity for 5-HT2C sites (Ki= 620 nM)[1][2][3][4].

  • CAS Number: 144734-36-1
  • MF: C24H28FNO5
  • MW: 429.48100
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CART (55-76) (rat) trifluoroacetate salt

CART (55-76), rat is a neuropeptide (55-76 residues of the CART peptide) and constitutes the N-terminal fragments of CART (55-102). CART (55-76), rat is a rat satiety factor with potent appetite-suppressing activity and is closely associated with leptin and neuropeptide Y. CART (55-76), rat can induce anxiety and stress-related behavior[1].

  • CAS Number: 1815618-15-5
  • MF: C107H166N26O33S3
  • MW: 2440.812
  • Catalog: Neuropeptide Y Receptor
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 2467.9±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 1446.4±34.3 °C

[cPP1-7,NPY19-23,Ala31,Aib32,Gln34]-hPancreatic Polypeptide

[cPP1-7,NPY19-23,Ala31,Aib32,Gln34]-hPancreatic Polypeptide is a potent and selective neuropeptide Y Y5 receptor agonist with an IC50 of 0.24 nM for binding to the hY5 receptor. [cPP1-7,NPY19-23,Ala31,Aib32,Gln34]-hPancreatic Polypeptide induces a high amount of food intake[1].

  • CAS Number: 313988-89-5
  • MF: C183H280N57O54S2
  • MW:
  • Catalog: Neuropeptide Y Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ambrisentan

Ambrisentan is a selective ET type A receptor (ETAR) antagonist.

  • CAS Number: 177036-94-1
  • MF: C22H22N2O4
  • MW: 378.42100
  • Catalog: Endothelin Receptor
  • Density: 1.228g/cm3
  • Boiling Point: 551.1ºC at 760mmHg
  • Melting Point: >150°C (dec.)
  • Flash Point: 287.1ºC

CORT 118335

CORT 118335 (Miricorilant, C118335) is a novel potent, selective, non-steroidal glucocorticoid receptor (GR) antagonist with Ki of 8 nM, shows modest affinity for MR.

  • CAS Number: 1400902-13-7
  • MF: C24H23F3N2O2
  • MW: 428.447
  • Catalog: Glucocorticoid Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ponesimod

Ponesimod(ACT-128800) is an orally active, selective sphingosine-1-phosphate receptor 1 (S1P1) immunomodulator.IC50 value: Target: S1P1 agonistin vitro: Ponesimod activated S1P(1)-mediated signal transduction with high potency (EC(50) of 5.7 nM) and selectivity [1]. in vivo: Oral administration of ponesimod to rats led to a dose-dependent decrease of blood lymphocyte count. After discontinuation of dosing, blood lymphocyte count returned to baseline within 48 h. Ponesimod prevented edema formation, inflammatory cell accumulation, and cytokine release in the skin of mice with delayed-type hypersensitivity [1].

  • CAS Number: 854107-55-4
  • MF: C23H25ClN2O4S
  • MW: 460.974
  • Catalog: LPL Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 658.0±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 351.7±34.3 °C

MK-6884

MK-6884 is a M4 muscarinic receptor positive allosteric modulator (PAM) with a Ki value of 0.19 nM. MK-6884 can be used for the research of the neurodegenerative diseases. MK-6884 can be conveniently radiolabeled with carbon-11 and as a positron emission tomography (PET) imaging agent[1].

  • CAS Number: 2102194-04-5
  • MF: C25H25N5O
  • MW: 411.50
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Dopamine D4 receptor antagonist-1

Dopamine D4 receptor antagonist-1 is a selective DRD4 antagonists, with a Ki of 9.0 nM for Hd4.2. Dopamine D4 receptor antagonist-1 can be used in study of schizophrenia[1].

  • CAS Number: 444724-92-9
  • MF: C18H19ClN4
  • MW: 326.82
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

WAY 161503 hydrochloride

(Rac)-WAY-161503 hydrochloride is a potent, selective, high affinity 5-HT2C receptor agonist with a Ki of 4 nM and an EC50 of 12 nM. (Rac)-WAY-161503 hydrochloride displays higher affinity for 5-HT2C than 5-HT2A and 5-HT2B receptors. (Rac)-WAY-161503 hydrochloride has anti-obesity and antidepressant effects[1][2].

  • CAS Number: 276695-22-8
  • MF: C11H12Cl3N3O
  • MW: 308.59
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Frovatriptan

Frovatriptan is a potent 5-HT1B//D receptor agonist and has the highest 5-HT1B potency in the triptan class. Frovatriptan is apparently cerebroselective. Frovatriptan is efficacious and even superior in some endpoints also when taken during the headache phase in migraine attacks with aura[1].

  • CAS Number: 158747-02-5
  • MF: C14H17N3O
  • MW: 243.30
  • Catalog: 5-HT Receptor
  • Density: 1.27g/cm3
  • Boiling Point: 515.2ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 265.4ºC

PSB 1115

PSB-1115 is a selective A2B Adenosine Receptor antagonist. PSB-1115 inhibits the 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced contraction inhibition of acetylcholine (ACh)[1].

  • CAS Number: 152529-79-8
  • MF: C14H14N4O5S
  • MW: 350.35000
  • Catalog: Adenosine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(Pyr5)-Substance P (5-11)

[Glp5] Substance P (5-11) is an octapeptide. [Glp5] Substance P (5-11) is one of the main substance P fragments in rat central nervous system (CNS). [Glp5] Substance P (5-11) locally modulates dopamine release in rat striatum[1].

  • CAS Number: 56104-22-4
  • MF: C41H57N9O9S
  • MW: 852.011
  • Catalog: Neurokinin Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 1374.9±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 785.3±34.3 °C

Anandamide-d11

Anandamide-d11 is deuterium labeled Anandamide. Anandamide is an immune modulator in the central nervous system acts via not only cannabinoid receptors (CB1 and CB2) but also other targets (e.g., GPR18/GPR55)[1][2].

  • CAS Number: 2260669-86-9
  • MF: C22H26D11NO2
  • MW: 358.60
  • Catalog: Cannabinoid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AS 2034178

AS2034178 free base, a specific and orally active GPR40 agonist, exhibits glucose-dependent insulin secretion enhancement. AS2034178 free base has potential for type 2 diabetes mellitus research[1].

  • CAS Number: 1030846-42-4
  • MF: C27H29FN2O3
  • MW: 448.52900
  • Catalog: GPR40
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 657.9±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 351.7±31.5 °C

ROS 234 dioxalate

ROS 234 dioxalate is a potent H3 antagonist, with a pKB of 9.46 for Guinea-pig ileum H3-receptor, a pKi of 8.90 for Rat cerebral cortex H3-receptor, and a ED50 of 19.12 mg/kg (ip) in ex vivo of Rat cerebral cortex. ROS 234 dioxalate diaplays poor central access[1][2].

  • CAS Number: 1781941-93-2
  • MF: C17H19N5O8
  • MW: 421.36
  • Catalog: Histamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

WAY-388264-A

5-HT2B antagonist-1 is an orally active 5-HT2B receptor antagonist with an IC50 value of 33.4 nM. 5-HT2B antagonist-1 can be used in studies of diseases characterized by 5-HT2B receptor signaling, such as hepatocellular carcinoma, cardiovascular disease or gastrointestinal disease[1][2].

  • CAS Number: 393129-91-4
  • MF: C11H14BrN5
  • MW: 296.17
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TT 232

TT-232 (CAP-232), a somatostatin derivative, is a peptide SSTR1/SSTR4 agonist. TT-232 inhibits cancer cell proliferation and induces apoptosis. TT-232 is also a broad-spectrum anti-inflammatory and analgesic agent[1][2][4].

  • CAS Number: 147159-51-1
  • MF: C22H32O2
  • MW: 328.48800
  • Catalog: Somatostatin Receptor
  • Density: 1.42g/cm3
  • Boiling Point: 1409.4ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 806.2ºC

FAA1 agonist-1

FAA1 agonist-1 is a potent free fatty acid receptor 1 (FFA1/ GPR40) agonist with a pEC50 of 7.54.

  • CAS Number: 2102196-57-4
  • MF: C21H17ClO5S
  • MW: 416.87
  • Catalog: GPR40
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AZD-5672

AZD-5672 is an orally active, potent, and selective CCR5 antagonist (IC50=0.32 nM). AZD-5672 shows moderate activity against the hERG ion channel (binding IC50=7.3 μM). AZD5672 is a substrate of human P-gp, and inhibits P-gp-mediated digoxin transport (IC50=32 μM). AZD-5672 can be used for the research of rheumatoid arthritis[1][2][3].

  • CAS Number: 780750-65-4
  • MF: C32H38F2N2O5S2
  • MW: 632.78100
  • Catalog: CCR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tropisetron hydrochloride

Tropisetron is a selective 5-HT3 receptor antagonist and α7-nicotinic receptor agonist with an IC50 of 70.1 ± 0.9 nM for 5-HT3 receptor.IC50 value: 70.1 ± 0.9 nMTarget: 5-HT3 receptor; α7-nicotinic receptorin vitro: Retinal ganglion cells(RGCs) pretreated with 100 nM tropisetron before glutamate increased cell survival to an average of 105% compared to controls. Inhibition studies using the alpha7 nAChR antagonist, MLA (10 nM), support the hypothesis that tropisetron is an effective neuroprotective agent against glutamate-induced excitotoxicity; mediated by α7 nAChR activation. Tropisetron had no discernible effects on pAkt levels but significantly decreased p38 MAPK levels associated with excitotoxicity from an average of 15 ng/ml to 6 ng/ml [2]. Tropisetron, but not granisetron, significantly inhibits the phosphatase activity of calcineurin, over-expresses the CB(1) receptors at both transcriptional and protein levels, and reduces cAMP content in cerebellar granule neurons (CGNs) [4].in vivo: Animals were treated intracerebroventricularly with tropisetron, mCPBG (selective 5-HT3 receptor agonist) or mCPBG plus tropisetron on days 1, 3, 5 and 7. Tropisetron significantly diminished the elevated levels of these markers and reversed the cognitive deficit. Interestingly, tropisetron was also found to be a potent inhibitor of calcineurin phosphatase activity [1]. tropisetron (5mg/kg/day) plus mCPBG (10mg/kg/day), and granisetron (5mg/kg/day) intraperitoneally on days 3-35 post-immunization. Treatment with tropisetron and granisetron markedly suppressed the clinical symptoms of EAE (p<0.001) and reduced leukocyte infiltration as well as demyelination in the spinal cord (p<0.05) [3].

  • CAS Number: 105826-92-4
  • MF: C17H21ClN2O2
  • MW: 320.814
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: 448.5ºC at 760 mmHg
  • Melting Point: 283-285ºC
  • Flash Point: 225ºC

Metipranolol hydrochloride

Metipranolol is a non-selective β adrenergic receptor blocking agent.

  • CAS Number: 36592-77-5
  • MF: C17H28ClNO4
  • MW: 345.86200
  • Catalog: Adrenergic Receptor
  • Density: N/A
  • Boiling Point: 484.5ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 246.8ºC

YNT-185

YNT-185 is a nonpeptide, selective orexin type-2 receptor (OX2R) agonist, with EC50s of 0.028 and 2.75 μM for OX2R and OX1R, respectively. YNT-185 ameliorates narcolepsy-cataplexy symptoms in mouse models[1][2].

  • CAS Number: 1804978-81-1
  • MF: C33H37N5O5S
  • MW: 615.74
  • Catalog: Orexin Receptor (OX Receptor)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ZK-90055 (hydrochloride)

ZK-90055 hydrochloride is a β2 adrenergic receptor agonist.

  • CAS Number: 84638-81-3
  • MF: C16H23ClN2O4
  • MW: 342.81800
  • Catalog: Adrenergic Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(R,R)-Reboxetine mesylate

(R,R)-Reboxetine mesylate is an antidepressant agent with great bioavailability. (R,R)-Reboxetine is the enantiomer of Reboxetine, which is a selective noradrenaline reuptake inhibitor. Reboxetine consists of (R,R) and (S,S) enantiomer, has low affinity for alpha-adrenergic and muscarinic receptors and low toxicity in animals[1][2].

  • CAS Number: 105017-39-8
  • MF: C20H27NO6S
  • MW: 409.50
  • Catalog: Adrenergic Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

naphazoline

Naphazoline (Naphthazoline) is a potent α-adrenergic receptor agonist. Naphazoline reduces vascular hyperpermeability and promotes vasoconstriction. Naphazoline reduces the levels of inflammatory factors (TNF-α, IL-1β and IL-6), cytokines (IFN-γ and IL-4), IgE, GMCSF, and NGF。Naphazoline can be used for non-bacterial conjunctivitis research[1][2].

  • CAS Number: 835-31-4
  • MF: C14H14N2
  • MW: 210.274
  • Catalog: Adrenergic Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 440.5±24.0 °C at 760 mmHg
  • Melting Point: 254ºC
  • Flash Point: 220.2±22.9 °C

4-(2-(PROPYLAMINO)ETHYL)INDOLIN-2-ONE

N-Despropyl Ropinirole (SKF-104557) is an active metabolite of the dopamine D2 receptor agonist Ropinirole (HY-B0623). N-Despropyl Ropinirole is a full agonist at human D2 and D3 receptors. N-Despropyl Ropinirole is a partial agonistof the hD4 receptor[1].

  • CAS Number: 106916-16-9
  • MF: C13H18N2O
  • MW: 218.29
  • Catalog: Dopamine Receptor
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 387.7±42.0 °C at 760 mmHg
  • Melting Point: 260-265ºC
  • Flash Point: 154.2±28.0 °C

Indacaterol-d3

Indacaterol-d3 is deuterium labeled Indacaterol.

  • CAS Number: 2699828-16-3
  • MF: C24H25D3N2O3
  • MW: 395.51
  • Catalog: Adrenergic Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SOS1-IN-12

SOS1-IN-12 is a potent son of sevenless homolog 1 (SOS1) inhibitor with a Ki of 0.11 nM for SOS1 and an IC50 of 47 nM for pERK. SOS1-IN-13 can be used for researching anticancer[1].

  • CAS Number: 2654741-56-5
  • MF: C23H26F3N5
  • MW: 429.48
  • Catalog: Ras
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Kos2602

kobe2602 is a novel and effective small-molecule compound inhibiting Ras–Raf interaction by SBDD; exhibits potent activity to competitively inhibit the binding of H-Ras·GTP to c-Raf-1 RBD with a Ki value of 149 ± 55 μM.IC50 value: 149 ± 55 uM (Ki) [1]Target: Ras-Raf These two compounds(Kobe0065 and Kobe2602), added to the culture medium at 2 and 20 μM, effectively reduced the amount of c-Raf-1 associated with H-Ras G12V in NIH 3T3 cells in a dose-dependent manner, indicating the inhibition of the cellular activity of Ras. A rough estimate of the IC50 value for the cellular Ras–Raf-binding inhibition was around 10 μM (Fig. 1B), which was not much different from the Ki values for the in vitro Ras–Raf-binding inhibition considering thequite low cellular concentration of Raf. A similar inhibitory effect was also observed with NIH 3T3 cells overexpressing K-Ras G12V. Both Kobe0065 and Kobe2602 at 20 μM efficiently inhibited the phosphorylation of MEK and ERK, downstream kinases of Raf in NIH 3T3 cells transiently expressingH-Ras G12V, although the effect was slightly weaker than that of2 μM sorafenib.

  • CAS Number: 454453-49-7
  • MF: C14H9F4N5O4S
  • MW: 419.311
  • Catalog: Ras
  • Density: 1.7±0.1 g/cm3
  • Boiling Point: 450.8±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 226.5±31.5 °C

2'-MeCCPA

2'-MeCCPA is a potent and selective A1 adenosine receptors (A1AR) agonist. 2'-MeCCPA efficiently inhibits cAMP modulation in both direct pathway medium spiny neurons (dMSNs) and indirect pathway medium spiny neurons (iMSNs)[1][2].

  • CAS Number: 205171-12-6
  • MF: C16H22ClN5O4
  • MW: 383.83000
  • Catalog: Adenosine Receptor
  • Density: 1.76g/cm3
  • Boiling Point: 643.3ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 342.9ºC