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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Olmesartan D4

Olmesartan D4 is the deuterium labeled Olmesartan. Olmesartan is an angiotensin II receptor (AT1R) antagonist used to treat high blood pressure.

  • CAS Number: 1420880-41-6
  • MF: C24H22D4N6O3
  • MW: 450.52600
  • Catalog: Angiotensin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

α-MSH trifluoroacetate salt

α-Melanocyte-Stimulating Hormone (MSH), amide stimulates melanocortin 1 receptor that results in the activation of adenylyl cyclase.

  • CAS Number: 581-05-5
  • MF: C77H109N21O19S
  • MW: 1664.884
  • Catalog: Peptides
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Amosulalol

Amosulalol (YM 09538) is an orally active and dual inhibitor of α1/β1-Adrenergic Receptor. Amosulalol exhibits antihypertensive activity via α1-Adrenergic Receptor inhibition. Amosulalol decreases reflexogenic increases in heart rate and plasma renin activity (PRA) via β1-Adrenergic Receptor inhibition in spontaneously hypertensive rats (SHR)[1].

  • CAS Number: 85320-68-9
  • MF: C18H24N2O5S
  • MW: 380.45900
  • Catalog: Adrenergic Receptor
  • Density: 1.268g/cm3
  • Boiling Point: 608.7ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 321.9ºC

Terodiline hydrochloride

Terodiline hydrochloride is an M1-selective muscarinic receptor (mAChR) antagonist with Kbs of 15, 160, 280, and 198 nM in rabbit vas deferens (M1), atria (M2), bladder (M3) and ileal muscle (M3), respectively. Terodiline hydrochloride also is a Ca2+ blocker. Terodiline hydrochloride acts as a treatment for urinary frequency and urge incontinence[1].

  • CAS Number: 7082-21-5
  • MF: C20H28ClN
  • MW: 317.89600
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: 390.9ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 168.9ºC

Almorexant

Almorexant(ACT078573) is a potent and competitive dual orexin 1 receptor (OX1)/orexin 2 receptor (OX2) antagonist with Ki values of 1.3 and 0.17 nM for OX1 and OX2, respectively.IC50 value: 1.3/0.7 nM(OX1/OX2 receptor) [1] [2]Target: Dual OX!/OX2 receptorin vitro: [(3)H]Almorexant bound to a single saturable site on hOX(1) and hOX(2) with high affinity (K(d) of 1.3 and 0.17 nM, respectively. In Schild analyses using the [(3)H]inositol phosphates assay, almorexant acted as a competitive antagonist at hOX(1) and as a noncompetitive-like antagonist at hOX(2). In binding kinetic analyses, [(3)H]almorexant had fast association and dissociation rates at hOX(1), whereas it had a fast association rate and a remarkably slow dissociation rate at hOX(2) [1]. in vivo: During the 12-h dark period after dosing, ALM(Almorexant) exacerbated cataplexy in TG mice and increased nonrapid eye movement sleep with heightened sleep/wake fragmentation in both genotypes. ALM showed greater hypnotic potency in WT mice than in TG mice. The 100 mg/kg dose conferred maximal promotion of cataplexy in TG mice and maximal promotion of REM sleep in WT mice. In TG mice, ALM (30 mg/ kg) paradoxically induced a transient increase in active wakefulness [3]. Almorexant 200 mg showed significantly less 'Drug Liking' than both zolpidem doses (p < 0.01), and almorexant 400 mg had smaller effects than zolpidem 20 mg (p < 0.05), while almorexant 1,000 mg was not different from either zolpidem dose [4].

  • CAS Number: 871224-64-5
  • MF: C29H31F3N2O3
  • MW: 512.563
  • Catalog: Orexin Receptor (OX Receptor)
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 620.4±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 329.0±31.5 °C

Fenoldopam hydrochloride

Fenoldopam (SKF 82526) hydrochloride is a D1 receptor agonist and a novel lysine-specific demethylase 1 (LSD1) inhibitor (IC50=0.8974 μM). Fenoldopam hydrochloride shows anti-hypertensive effects, anti-cancer cell proliferation activity and can induce cells apoptosis[1][2][3].

  • CAS Number: 181217-39-0
  • MF: C16H17Cl2NO3
  • MW: 342.22
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Chlorpromazine-d6 Hydrochloride

Chlorpromazine D6 hydrochloride is the deuterium labeled Chlorpromazine. Chlorpromazine is an inhibitor of dopamine receptor, 5-HT receptor, potassium channel, sodium channel.

  • CAS Number: 1228182-46-4
  • MF: C17H14D6Cl2N2S
  • MW: 361.36
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 187-189°C
  • Flash Point: N/A

VU 0467485

VU0467485 (VU-0467485, AZ13713945) is potent, selective, and orally bioavailable muscarinic acetylcholine receptor 4 (M4) positive allosteric modulator with EC50 of 78.8 nM (hM4); possesses robust in vitro M4 PAM potency across species and in vivo efficacy in preclinical models of schizophrenia.

  • CAS Number: 1451994-10-7
  • MF: C17H17FN4O2S
  • MW: 360.406
  • Catalog: mAChR
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

2-Chloro-N-[(6-{[3-(4-methyl-1-piperazinyl)propyl]sulfonyl}-1,3-benzothiazol-2-yl)carbamoyl]-5-(4-morpholinyl)benzamide

AZ-GHS-22 is a potent, non-CNS penetrant GHS-R1a inverse agonist (IC50=0.77 nM)[1].

  • CAS Number: 1143020-91-0
  • MF: C27H33ClN6O5S2
  • MW: 621.171
  • Catalog: GHSR
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(±)-Tazifylline

(±)-Tazifylline is a potent, selective and long-acting histamine H1 receptor antagonist.

  • CAS Number: 79712-55-3
  • MF: C23H32N6O3S
  • MW: 472.60400
  • Catalog: Histamine Receptor
  • Density: 1.34g/cm3
  • Boiling Point: 705.1ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 380.2ºC

KRAS G12C inhibitor 27

KRAS G12C inhibitor 27 is a KRAS G12C inhibitor with antitumor effects (WO2021109737)[1].

  • CAS Number: 2648584-51-2
  • MF: C29H32F4N6O3
  • MW: 588.60
  • Catalog: Ras
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

VU0357017

VU0357017 hydrochloride is a highly selective M1 agonists that appear to act at an allosteric site to activate the receptor (EC50 = 477 ± 172 nM; pEC50 = 6.37 ± 0.15).IC50 value: 477 ± 172 nM (EC50) [1]Target: M1in vitro: VU0357017 is a M1-selective agonists that appear to activate M1 through actions at an allosteric site. Ki values of VU0357017 derived from competition binding experiment is 9.91(rM1), 21.4 (rM2), 55.3 (rM3), 35 (rM4), and 50 (rM5), respectively. [1] VU0357017 is a potent and efficacious M1 agonist, selective versus M2 M5 family members and allosteric agonist. VU0357017 is a highly selective M1 agonist suggests that these compounds are unlikely to act at the highly conserved orthosteric site on M1 and are more likely to act as allosteric agonists. [2] VU0357017 has robust effects on M1-activation of calcium mobilization and ERK1/2 phosphorylation but have little effect on β-arrestin recruitment. VU0357017 induces calcium release and ERK phosphorylation but is without effects on β-arrestin recruitment. VU0357017 significantly enhances threshold Θ-burst LTP and VU0364572 induces LTD at the Schaffer collateral-CA1 synapse of rodent hippocampal slices. [3]in vivo: VU0357017 has robust efficacy in improving hippocampal-dependent learning in rats. VU0357017 enhances performance in Morris water maze and contextual fear conditioning in rats. [3]

  • CAS Number: 1135242-13-5
  • MF: C18H28ClN3O3
  • MW: 369.88600
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

μ opioid receptor agonist 3

μ opioid receptor agonist 3 (compound 20) is a potent μ opioid receptor (µOR) agonist with an EC50 of 0.87 nM. μ opioid receptor agonist 3 has the potential for pain and neuropsychiatric indications research[1].

  • CAS Number: 2378397-91-0
  • MF: C22H28N2O2
  • MW: 352.47
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Hemopressin (human, mouse)

Hemopressin is a nonapeptide derived from the α1-chain of hemoglobin, is originally isolated from rat brain homogenates. Hemopressin is orally active, selective and inverse agonist of CB1 cannabinoid receptors. Hemopressin exerts antinociceptive action in inflammatory pain models[1][2].

  • CAS Number: 1314035-51-2
  • MF: C50H79N13O12
  • MW: 1054.242
  • Catalog: Cannabinoid Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 1491.3±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 855.7±34.3 °C

(Asn1,Val5)-Angiotensin II

Angiotensin amide ((Asn1,Val5)-Angiotensin II) is a potent vasoconstrictor. Angiotensin amide is a derivative of angiotensin II. Angiotensin amide can be used as a cardiac stimulant[1].

  • CAS Number: 53-73-6
  • MF: C49H70N14O11
  • MW: 1031.17000
  • Catalog: Angiotensin Receptor
  • Density: 1.45g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

KRas G12C inhibitor 1

KRas G12C inhibitor 1 is a compound that inhibits KRas G12C, extracted from patent US 20180072723 A1.

  • CAS Number: 2158297-28-8
  • MF: C31H38N6O3
  • MW: 542.67
  • Catalog: Ras
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

P2Y2R/GPR17 antagonist 1

P2Y2R/GPR17 antagonist 1 (Compound 14m) is a dual P2Y2R and GPR17 antagonist with IC50 values of 3.17 µM and 1.67 µM against P2Y2R and GPR17, respectively. P2Y2R/GPR17 antagonist 1 shows excellent metabolic stability in human liver microsomes[1].

  • CAS Number: 2395016-49-4
  • MF: C19H13ClN2O6S
  • MW: 432.83
  • Catalog: P2Y Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Lesopitron (dihydrochloride)

Lesopitron dihydrochloride is a full and selective 5-HT1A receptor agonist with IC50 of 125 nM in rat hippocampal membranes.

  • CAS Number: 132449-89-9
  • MF: C15H23Cl3N6
  • MW: 393.74200
  • Catalog: 5-HT Receptor
  • Density: 1.31g/cm3
  • Boiling Point: 504ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 258.6ºC

Ki16198

Ki16198 is a potent and orally active LPA receptor antagonist, the methyl ester of Ki16425 (HY-13285). Ki16198 inhibits LPA1 and LPA3-induced inositol phosphate production with Ki values of 0.34 μM and 0.93 μM, respectively. Ki16198 is effective for pancreatic cancer tumorigenesis and metastasis in vivo[1].

  • CAS Number: 355025-13-7
  • MF: C24H25ClN2O5S
  • MW: 488.984
  • Catalog: LPL Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 594.2±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 313.2±30.1 °C

Neuropeptide Y (13-36) (human, rat) trifluoroacetate salt

Neuropeptide Y (13-36), amide, human is a neuropeptide Y receptor agonist.

  • CAS Number: 122341-40-6
  • MF: C134H207N41O36S
  • MW: 3000.40000
  • Catalog: Peptides
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Phenglutarimid

Phenglutarimid is an anticholinergic used as an antiparkinsonian agent.

  • CAS Number: 1156-05-4
  • MF: C17H24N2O2
  • MW: 288.38500
  • Catalog: mAChR
  • Density: 1.072g/cm3
  • Boiling Point: 447.8ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 224.6ºC

Dehydro Olmesartan

Dehydro Olmesartan is a derivative of Olmesartan. Olmesartan is an angiotensin II receptor (AT1R) antagonist and has the potential for high blood pressure study[1][2].

  • CAS Number: 172875-98-8
  • MF: C24H24N6O2
  • MW: 428.48600
  • Catalog: Angiotensin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

9-fluorenol

9-Fluorenol (9-Hydroxyfluorene; compound 3) is a dopamine (DAT) inhibitor with IC50 value of 9 µM. 9-Fluorenol is a major metabolite of compound developed as a wake promoting agent. 9-Fluorenol shows wake promotion activity in vivo[1].

  • CAS Number: 1689-64-1
  • MF: C13H10O
  • MW: 182.218
  • Catalog: Dopamine Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 367.5±11.0 °C at 760 mmHg
  • Melting Point: 153-154 °C(lit.)
  • Flash Point: 131.3±11.5 °C

AB-MECA

AB-MECA is a high affinity A3 adenosine receptor agonist, has high affinity for recombinant A1 and A3 receptors.

  • CAS Number: 152918-26-8
  • MF: C18H21N7O4
  • MW: 399.40400
  • Catalog: Adenosine Receptor
  • Density: 1.68g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Glucocorticoids receptor agonist 1

Glucocorticoids receptor agonist 1 is a potent anti-inflammatory, arylpyrazole-based glucocorticoid receptor agonist that does not impair insulin secretion.

  • CAS Number: 694526-54-0
  • MF: C20H23FN2O
  • MW: 326.41
  • Catalog: Glucocorticoid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

RS 102221

RS-102221 hydrochloride is a selective 5-HT2C receptor antagonist (Ki=10 nM). RS-102221 hydrochloride shows nearly 100-fold selectivity for the 5-HT2C receptor as compared to the 5-HT2A and 5-HT2B receptors. RS-102221 hydrochloride can promote the differentiation of new nerve cells. RS-102221 hydrochloride increases food-intake and weight-gain in rats[1][2].

  • CAS Number: 187397-18-8
  • MF: C27H32ClF3N4O7S
  • MW: 649.079
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Sarafotoxin A

Sarafotoxin S6a, a sarafotoxin analogue, is a endothelin receptor agonist and has an ETA/ETB selectivity profile similar to that of Endothelin-3 (HY-P0204). Sarafotoxin S6a elicits the pig coronary artery with an EC50 value of 7.5 nM[1].

  • CAS Number: 126738-34-9
  • MF: C105H156N28O34S5
  • MW: 2514.85000
  • Catalog: Endothelin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Boc-Ala-Ala-D-Trp-Phe-D-Pro-Pro-NleNH2

GR 87389 is a potent NK2 receptor antagonist. GR 87389 antagonized GA 64349-induced smooth muscle strips contractions in a competitive manner in the human detrusor, prostate and prostatic urethra[1][2].

  • CAS Number: 141663-86-7
  • MF: C47H65N9O9
  • MW: 900.07400
  • Catalog: Neurokinin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SKF-83566

SKF-83566 is a potent, blood-brain permeable and orally active D1-like dopamine receptor (D1DR) antagonist and a weaker competitive antagonist at the vascular 5-HT2 receptor (Ki=11 nM)[1][3]. SKF-83566 is a competitive DAT (dopamine transporter) inhibitor with an IC50 of 5.7 μM[2]. SKF-83566 also shows selective inhibition for adenylyl cyclase 2 (AC2) over AC1 and AC5 in the isolated rabbit thoracic aorta[4]. SKF-83566 can be used for research of parkinson’s disease and nicotine craving alleviation[5].

  • CAS Number: 99295-33-7
  • MF: C17H19BrClNO
  • MW: 368.69600
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: 447.5ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 224.4ºC

CCK-B Receptor Antagonist 1

CCK-B Receptor Antagonist 1 is an antagonist of cholecystokinin B (CCK-B) receptor, and has the potential of reducing the secretion of gastric acid.

  • CAS Number: 168161-71-5
  • MF: C28H30N6O3
  • MW: 498.58
  • Catalog: Cholecystokinin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A