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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TC-G 1006

S1P1 Agonist III is a potent and orally active S1P1 agonist with EC50 of 18 nM; no activity on S1P3.IC50 value: 18 nM(EC50) [1]Target: S1P1 agonistWhen dosed orally at 1 and 3 mg/kg, the azahydroxymethyl analogue 22(HY-12835) achieved statistically significant lowering of circulating blood lymphocytes 24 h postdose. In rats, a dose-proportional increase in exposure was measured when 22(HY-12835) was dosed orally at 2 and 100 mg/kg. 22 displayed excellent pharmacokinetic parameters with low clearance (CL = 0.11 L/h/kg), long mean residence time (40 h), and good oral bioavailability (F = 67%).

  • CAS Number: 1324003-64-6
  • MF: C21H16F3N3O3
  • MW: 415.36500
  • Catalog: LPL Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BMS-986278

BMS-986278 is a potent lysophosphatidic acid receptor 1 (LPA1) antagonist, with a human LPA1 Kb of 6.9 nM.

  • CAS Number: 2170126-74-4
  • MF: C22H31N5O5
  • MW: 445.51
  • Catalog: LPL Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CORT-108297

Cort108297 is a specific glucocorticoid receptor (GR) antagonist. Cort108297 has a high affinity for GRs with a Ki of 0.45 nM.

  • CAS Number: 1018679-79-2
  • MF: C26H25F4N3O3S
  • MW: 535.55400
  • Catalog: Glucocorticoid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CP-96345

CP-96,345 is a specific, highly potent, and orally active tachykinin and substance P receptor non-peptide inhibitor. CP-96,345 prevents the drop in blood pressure evoked by substance P and neurokinin A. CP-96,345 can be used for researching neurogenic inflammation[1].

  • CAS Number: 132746-60-2
  • MF: C28H32N2O
  • MW: 412.57
  • Catalog: Neurokinin Receptor
  • Density: 1.15g/cm3
  • Boiling Point: 541.5ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 281.3ºC

Irbesartan hydrochloride

Irbesartan (SR-47436) hydrochloride is an orally active Ang II type 1 (AT1) receptor blocker (ARB). Irbesartan hydrochloride can relax the blood vessels, low blood pressure and increase the supply of blood and oxygen to the heart. Irbesartan hydrochloride can be used for the research of high blood pressure, heart failure, and diabetic kidney disease[1].

  • CAS Number: 329055-23-4
  • MF: C25H29ClN6O
  • MW: 464.99000
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ARC 239 dihydrochloride

ARC 239 dihydrochloride is a selective α2B/2C adrenoceptor antagonist (pKd values are 5.95, 7.41 and 7.56 at α2A, α2B, and α2C receptors respectively). ARC 239 dihydrochloride binds to CHO cell membranes expressing human recombinant a2A-, a2B- or a2C-adrenoceptor subtypes with pKis of 5.6, 8.4, and 7.08, respectively[1].

  • CAS Number: 55974-42-0
  • MF: C24H31Cl2N3O3
  • MW: 480.42700
  • Catalog: Adrenergic Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

L-798106

L-798106 is potent and highly selective prostanoid EP3 receptor antagonist (Ki=0.3 nM), it also has  micromolar activities at the EP4, EP1 and EP2 receptors with Ki values of 916 nM, >5000 nM and >5000 nM at EP4, EP1 and EP2, respectively[1].

  • CAS Number: 244101-02-8
  • MF: C27H22BrNO4S
  • MW: 536.43700
  • Catalog: Prostaglandin Receptor
  • Density: 1.425±0.06 g/cm3(Predicted)
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Valsartan D9

Valsartan D9 (CGP-48933 D9) is deuterium labeled valsartan. Valsartan is an angiotensin II receptor antagonist for treatment of high blood pressure and heart failure.

  • CAS Number: 1089736-73-1
  • MF: C24H20D9N5O3
  • MW: 444.57400
  • Catalog: Angiotensin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Nizatidine

Nizatidine is a histamine H2 receptor antagonist with low toxicity that inhibits gastric acid secretion.Target: Histamine H2 ReceptorNizatidine, a selective histamine H2-receptor antagonist, is a potent inhibitor of gastric acid secretion, with IC50 of 0.9 nM. Nizatidine exhibits maximal inhibition of gastric acid in rats within the first hour of drug administration, with EC50 of 1.383 μmol/kg [1]. Nizatidine also reversibly inhibits acetylcholinesterase (AChE), with IC50 of 6.7 μM, and the inhibition is noncompetitive, with a Ki value of 7.4 μM. Nizatidine (0.3-3 mg/kg, i.v.) significantly increases the motor index of gastrointestinal (GI) motility in a dose-dependent manner. Nizatidine inhibits gastric acid secretion with ED50 and ED90 of 0.18 and 3.22 mg/kg in dogs, and 2.94 and 19.6 mg/kg in rats, respectively [2].

  • CAS Number: 76963-41-2
  • MF: C12H21N5O2S2
  • MW: 331.457
  • Catalog: Histamine Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 478.2±45.0 °C at 760 mmHg
  • Melting Point: 130-132ºC
  • Flash Point: 243.0±28.7 °C

Riociguat

Riociguat is an oral stimulator of soluble guanylate cyclase (sGC) used in the treatment of pulmonary hypertension.

  • CAS Number: 625115-55-1
  • MF: C20H19FN8O2
  • MW: 422.416
  • Catalog: Guanylate Cyclase
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 567.2±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 296.8±30.1 °C

3-[2-[4-(3,4-dimethylphenyl)-1-piperazinyl]ethyl]-2,3-dihydro-1H-isoindol-1-onedihydrochloride

PD 168568 is a orally active and potent dopamine receptor D4 (DRD4) antagonist. PD 168568 contains an isoindolinone and is selective for the D4 receptor versus D2 and D3, with Ki values of 8.8, 1842, and 2682 nM, respectively. PD 168568 can be used for glioblastoma (GBM) research[1][2].

  • CAS Number: 210688-56-5
  • MF: C22H29Cl2N3O
  • MW: 422.39100
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

D4R agonist-1

D4R agonist-1 (Compound 16f) is a D4R partial agonist (Ki: 2.2 nM). D4R agonist-1 is metabolically stable in rat and human liver microsomes. D4R agonist-1 can be used for research of neuropsychiatric disorders[1].

  • CAS Number: 2826198-44-9
  • MF: C19H22N4S
  • MW: 338.47
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

homatropine hydrochloride

Homatropine hydrochloride is an orally active anticholinergic agent that rapidly dilates pupils and has cycloplegic effects. Homatropine hydrochloride also has antitussive activity. Homatropine hydrochloride can be used in research on eye diseases and coughs[1].

  • CAS Number: 637-21-8
  • MF: C16H22ClNO3
  • MW: 311.80
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: 403.3ºC at 760 mmHg
  • Melting Point: 226ºC
  • Flash Point: 197.7ºC

Wy 49051

Wy 49051 is a potent, orally active H1 receptor antagonist, with IC50 of 44 nM.

  • CAS Number: 113418-56-7
  • MF: C28H33N5O3
  • MW: 487.59
  • Catalog: Histamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BMS-986020 sodium

BMS-986020 sodium is a high-affinity lysophosphatidic acid receptor 1 (LPA1) antagonist[1].BMS-986020 sodium inhibits bile acid and phospholipid transporters with IC50s of 4.8 µM, 6.2 µM, and 7.5 µM for BSEP, MRP4, and MDR3, respectively[2]. BMS-986020 sodium is used for the treatment of idiopathic pulmonary fibrosis (IPF)[3].

  • CAS Number: 1380650-53-2
  • MF: C29H25N2NaO5
  • MW: 504.51
  • Catalog: LPL Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

S38093 HCl

S 38093 hydrochloride is a brain-penetrant, orally active antagonist of H3 receptor, with Kis of 8.8, 1.44 and 1.2 µM for rat, mouse and human H3 receptors, respectively.

  • CAS Number: 1222097-72-4
  • MF: C17H25ClN2O2
  • MW: 324.85
  • Catalog: Histamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Nipradilol

Nipradolol (KT-210; K-351) is a potent blocker of alpha-1-adrenergic receptors. Nipradolol inhibits the increase of intraocular pressure (IOP) in an albino rabbit model induced by Phenylephrine (HY-B0769). Nipradolo suppresses the noradrenaline (NA)-induced muscles contraction, also exhibits vasodilator activity on the dog coronary artery[1][2].

  • CAS Number: 81486-22-8
  • MF: C15H22N2O6
  • MW: 326.345
  • Catalog: Adrenergic Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 500.0±45.0 °C at 760 mmHg
  • Melting Point: 110-122ºC
  • Flash Point: 256.2±28.7 °C

Sunobinop

Sunobinop (S 117957) is a modulator of the opioid receptor-like orphan receptor (ORL1)[1].

  • CAS Number: 1126793-40-5
  • MF: C26H33N3O3
  • MW: 435.56
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

KRAS G12C inhibitor 31

KRAS G12C inhibitor 31 is a KRAS G12C inhibitor extracted from patent WO2021252339A1, compound 1. KRAS G12C inhibitor 31 can be used for the research of cancer[1].

  • CAS Number: 2752352-86-4
  • MF: C25H22ClFN6O3
  • MW: 508.93
  • Catalog: Ras
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JNJ-10229570

JNJ-10229570 is an antagonist of melanocortin receptor 1 (MC1R) and melanocortin receptor 5 (MC5R), which inhibits sebaceous gland differentiation and the production of sebum-specific lipids. JNJ-10229570 inhibits the binding of 125I-NDP-α-MSH to cells expressing human MC1R and MC5R, with IC50 values of 270 nM and 200 nM, respectively.

  • CAS Number: 524923-88-4
  • MF: C22H19N3O2S
  • MW: 389.47000
  • Catalog: Others
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GLP-2 (human)

GLP-2(1-33) (human) is an enteroendocrine hormone which can bind to the GLP-2 receptor and stimulate the growth of intestinal epithelium.

  • CAS Number: 223460-79-5
  • MF: C126H207N37O34S
  • MW: 2816.28
  • Catalog: Peptides
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BA 1

BA 1 is a potent bombesin receptor agonist (IC50 values are 0.26, 1.55 and 2.52 nM for BB1, BB2 and BB3 respectively). BA 1 enhances glucose transport in obese and diabetic primary myocytes. BA 1 also stimulates NCI-H1299 lung cancer cell proliferation in vitro.

  • CAS Number: 183241-31-8
  • MF: C57H76N14O11
  • MW: 1133.30
  • Catalog: Bombesin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

dynorphin (1-11), Pro(10)-

[DPro10] Dynorphin A (1-11), porcine, a N-Alkylated derivative, is a potent κ-opioid receptor agonist with a Ki value of 0.13 nM. [DPro10] Dynorphin A (1-11), porcine has analgesic property[1][2].

  • CAS Number: 94596-26-6
  • MF: C63H103N21O13
  • MW: 1362.62000
  • Catalog: Adenylate Cyclase
  • Density: 1.42±0.1 g/cm3 (20 °C, 760 mmHg)
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Adenosine antagonist-1

Adenosine antagonist-1 is an adenosine A3 receptor (AA3R) antagonist.

  • CAS Number: 431040-19-6
  • MF: C18H13N7S
  • MW: 359.41
  • Catalog: Adenosine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

6H05

6H05 is a selective, and allosteric inhibitor of oncogenic mutant K-Ras(G12C). IC50 value:Target: K-Ras G12C6H05 gives the greatest degree of modification, which allosterically modifies the oncogenic G12C mutant of highly homologous protein H-Ras without affecting wild-type K-Ras [1]. 6H05 can be used as an intermediate for the synthesis of other oncogenic K-Ras(G12C) inhibitors [2].

  • CAS Number: 1469338-01-9
  • MF: C20H30ClN3O2S3
  • MW: 476.12
  • Catalog: Ras
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 735.5±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 398.6±35.7 °C

E-3620

E-3620 is a potent 5-HT3 receptor antagonist. E-3620 can be used for the research of dyskinesi and gastrointestinal motility[1][2].

  • CAS Number: 151213-86-4
  • MF: C20H27Cl2N3O2
  • MW: 412.35
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MAO-A/5-HT2AR-IN-1

MAO-A/5-HT2AR-IN-1 (compound I14) is a potent MAO-A and 5-HT2AR dual inhibitor, with IC50 values of 0.004 and 0.014 μM, respectively. MAO-A/5-HT2AR-IN-1 is a potential antidepressant agent[1].

  • CAS Number: 2769156-00-3
  • MF: C30H28FN3O2
  • MW: 481.56
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Lenperone Hydrochloride

Lenperone hydrochloride (AHR 2277) is an antipsychotic compound and a dopamine antagonist. Lenperone hydrochloride reduces gastroesophageal sphincter pressure of healthy dogs. Lenperone hydrochloride can be used for neurological disease research[1][2].

  • CAS Number: 24677-86-9
  • MF: C22H24ClF2NO2
  • MW: 407.88100
  • Catalog: Dopamine Receptor
  • Density: 1.186g/cm3
  • Boiling Point: 507.9ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 261ºC

Deltorphin

Deltorphin (Deltorphin A; Dermenkephalin) is a biological active peptide. (Deltorphin A peptide was isolated from skin extracts of the South American frog, Phyllomedusa sauvagei. Deltorphin A is a potent and selective agonist for the delta-opioid receptor.)

  • CAS Number: 119975-64-3
  • MF: C44H62N10O10S2
  • MW: 955.15
  • Catalog: Opioid Receptor
  • Density: 1.317g/cm3
  • Boiling Point: 1425.7ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 816ºC

Eletriptan HBr

Eletriptan HBr is a selective 5-HT1B and 5-HT1D receptor agonist with Ki of 0.92 nM and 3.14 nM, respectively.IC50 value: 0.82 nM/3.14 nM (5-HT1B/5-HT1D, Ki) [1]Target: 5-HT1B/5-HT1D in vitro: [3H]Eletriptan has a total number of binding sites (Bmax) of 2478 fmol/mg and 1576 fmol/mg for 5-HT1B and 5-HT1D, respectively. [3H]Eletriptan has a significantly faster association rate (K(on) 0.249/min/nM) than [3H]sumatriptan (K(on) 0.024/min/nM) and a significantly slower off-rate (K(off) 0.027/min compared to 0.037/min for [3H]sumatriptan) [1]. Eletriptan induces concentration-dependent contractions of meningeal artery, coronary artery, and saphenous vein. The potency of Eletriptan is higher in meningeal artery than in coronary artery (86-fold) or saphenous vein (66-fold). The predicted contraction by Eletriptan (40 mg and 80 mg) and sumatriptan (100 mg) at free C(max) observed in clinical trials is similar in meningeal artery [2].in vivo: Eletriptan (<1000 mg/kg, i.v.) produces a dose-dependent reduction of carotid arterial blood flow in the anaesthetised dog. Eletriptan reduces coronary artery diameter with ED50 value of 63 mg/kg in the anaesthetised dog. Eletriptan (<300 mg/kg, i.v.) administered prior to electrical stimulation of the trigeminal ganglion produces a dose-related and complete inhibition of plasma protein extravasation in the dura mater rats. Eletriptan (100 mg/kg, i.v.) produces a complete inhibition of plasma protein extravasation in rat dura mater [3]. Iontophoretic ejection (50 nA) of Eletriptan suppresses the response in 75% of cells and causes an average suppression of cell firing of 42% in cats [4].

  • CAS Number: 177834-92-3
  • MF: C22H27BrN2O2S
  • MW: 463.43
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: 633.9ºC at 760 mmHg
  • Melting Point: 169-171ºC
  • Flash Point: 337.2ºC