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.


Anti-infection >
Arenavirus Bacterial CMV Enterovirus Filovirus Fungal HBV HCV HIV HSV Influenza Virus Parasite Reverse Transcriptase RSV SARS-CoV
Antibody-drug Conjugate >
ADC Cytotoxin ADC Linker Drug-Linker Conjugates for ADC PROTAC-linker Conjugate for PAC
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15-PGDH 5 alpha Reductase 5-Lipoxygenase Acetyl-CoA Carboxylase Acyltransferase Adenosine Deaminase Adenosine Kinase Aldehyde Dehydrogenase (ALDH) Aldose Reductase Aminopeptidase Angiotensin-converting Enzyme (ACE) ATGL ATP Citrate Lyase Carbonic Anhydrase Carboxypeptidase Cathepsin CETP COMT Cytochrome P450 Dipeptidyl Peptidase Dopamine β-hydroxylase E1/E2/E3 Enzyme Elastase Enolase FAAH FABP Factor Xa Farnesyl Transferase Fatty Acid Synthase (FAS) FXR Glucokinase GSNOR Gutathione S-transferase HCV Protease Hexokinase HIF/HIF Prolyl-Hydroxylase HIV Integrase HIV Protease HMG-CoA Reductase (HMGCR) HSP Indoleamine 2,3-Dioxygenase (IDO) Isocitrate Dehydrogenase (IDH) Lactate Dehydrogenase LXR MAGL Mineralocorticoid Receptor Mitochondrial Metabolism MMP Nampt NEDD8-activating Enzyme Neprilysin PAI-1 PDHK PGC-1α Phosphatase Phosphodiesterase (PDE) Phospholipase Procollagen C Proteinase Proteasome Pyruvate Kinase RAR/RXR Renin ROR Ser/Thr Protease SGK Stearoyl-CoA Desaturase (SCD) Thrombin Tryptophan Hydroxylase Tyrosinase Xanthine Oxidase
Neuronal Signaling >
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CB1R Allosteric modulator 3

CB1R Allosteric modulator 3, a novel analogs derived from the 2-phenylindole scaffold, is a CB1R positive allosteric modulator. CB1R Allosteric modulator 3 has potent inhibition of cAMP and β-Arrestin with EC50 values of 0.018 μM and 1.241 μM[1].

  • CAS Number: 2633686-36-7
  • MF: C22H17ClN2O2
  • MW: 376.84
  • Catalog: Cannabinoid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Alvimopan

Alvimopan dihydrate(LY 246736; ADL 8-2698) is a peripherally acting mu-opioid receptor (PAM-OR, IC50= 1.7 nM) antagonist for accelerating gastrointestinal recovery after surgery. IC50 Value: 1.7 nM (Mu-type opioid receptor) [1]Target: mu-opioid receptorin vitro: The dissociation rate of alvimopan from the micro opioid receptor (t(1/2)=30--44 min) was comparable to that of the long acting partial agonist buprenorphine (t(1/2)=44 min), but was slower than those of the antagonists naloxone (t(1/2)=0.82 min) and N-methylnaltrexone (t(1/2)=0.46 min) [2].in vivo: Alvimopan did not significantly accelerate GI-3 compared with placebo [6 mg: hazard ratio (HR) = 1.20, p = 0.080; 12 mg: HR = 1.24, p = 0.038). However, after adjustment for significant covariates (sex/surgical duration), benefits were significant for both doses (6 mg: HR = 1.24, p = 0.037; 12 mg: HR = 1.26, p = 0.028). Alvimopan also significantly accelerated time to GI-2 (6 mg: HR = 1.37, p = 0.008; 12 mg: HR = 1.33, p = 0.018) and DCO (6 mg: HR = 1.31, p = 0.008; 12 mg: HR = 1.28, p = 0.015) [3]. Alvimopan (1 and 3 mg/kg) significantly reversed this delayed GI transit when administered 45 min prior to surgery. However, the effects of alvimopan were less pronounced when administered following surgery [4].Toxicity:The most common treatment-emergent adverse events across all treatment groups were nausea, vomiting, and hypotension; the incidence of nausea and vomiting was reduced by 53 percent in thealvimopan 12-mg group [5].Clinical trial: Intercostal Nerve Block With Liposome Bupivacaine in Subjects Undergoing Posterolateral Thoracotomy. Phase 3

  • CAS Number: 170098-38-1
  • MF: C25H36N2O6
  • MW: 460.563
  • Catalog: Opioid Receptor
  • Density: 1.166g/cm3
  • Boiling Point: 684.1ºC at 760mmHg
  • Melting Point: 210-213ºC
  • Flash Point: 367.5ºC

KRAS G12C inhibitor 37

KRAS G12C inhibitor 37 is a potent inhibitor of KRAS G12C. The Ras family of proteins is an important intracellular signaling molecule that plays an important role in growth and development. KRAS G12C inhibitor 37 has the potential for the research of KRAS G12C-mediated cancer (extracted from patent WO2018143315A1, compound 65)[1].

  • CAS Number: 2241720-04-5
  • MF: C35H39F3N8O2
  • MW: 660.73
  • Catalog: Ras
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Clomipramine-d3 (hydrochloride)

Clomipramine D3 hydrochloride is a deuterium labeled Clomipramine hydrochloride. Clomipramine hydrochloride is a serotonin transporter (SERT), norepinephrine transporter (NET) dopamine transporter (DAT) blocker with Ki of 0.14, 54 and 3 nM, respectively[1][2].

  • CAS Number: 1398065-86-5
  • MF: C19H21D3Cl2N2
  • MW: 354.332
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: 9℃

pimozide

Pimozide is a dopamine receptor antagonist, with Kis of 1.4 nM, 2.5 nM and 588 nM for dopamine D2, D3 and D1 receptors, respectively, and also has affinity at α1-adrenoceptor, with a Ki of 39 nM; Pimozide also inhibits STAT3 and STAT5.

  • CAS Number: 2062-78-4
  • MF: C28H29F2N3O
  • MW: 461.546
  • Catalog: Adrenergic Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 649.0±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 346.3±34.3 °C

TT-OAD2

TT-OAD2 is a non-peptide glucagon-like peptide-1 (GLP-1) receptor agonist with an EC50 of 5 nM. TT-OAD2 has the potential for diabetes treatment[1][2].

  • CAS Number: 2382719-60-8
  • MF: C50H49Cl4N3O6
  • MW: 929.75
  • Catalog: Glucagon Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GR 64349

GR 64349 is a potent and highly selective NK2 receptor peptide antagonist, with an EC50 of 3.7 nM in rat colon. GR 64349 exhibits selectivity >1000 and >300-fold with respect to NK1 and NK3 receptors, respectively[1][2].

  • CAS Number: 137593-52-3
  • MF: C42H68N10O11S
  • MW: 921.11500
  • Catalog: Neurokinin Receptor
  • Density: 1.31g/cm3
  • Boiling Point: 1342.8ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 765.9ºC

4-[3-(2-chloro-10H-phenothiazin-10-yl)propyl]piperazine-1-ethanol dihydrochloride

Perphenazine dihydrochloride is an orally active dopamine receptor and histamine-1 receptor antagonist, with Ki values of 0.56 nM (D2), 0.43 nM (D3), .6 nM (5-HT2A), respectively. Perphenazine dihydrochloride also binds to Alpha-1A adrenergic receptor. Perphenazine dihydrochloride inhibits cancer cell proliferation, and induces apoptosis. Perphenazine dihydrochloride can be used in the research of mental disease, cancer, inflammation[1][3][5].

  • CAS Number: 2015-28-3
  • MF: C21H28Cl3N3OS
  • MW: 476.89100
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: 580.4ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 304.8ºC

BGC-20-1531 free base

BGC-20-1531 (PGN 1531) free base is a potent and selective prostanoid EP4 receptor antagonist, with a pKb of 7.6. BGC-20-1531 free base has the potential for the research of migraine headache[1].

  • CAS Number: 736183-35-0
  • MF: C26H24N2O6S
  • MW: 492.54
  • Catalog: Prostaglandin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Solifenacin hydrochloride

Solifenacin Hcl(YM905 Hcl; Vesicare Hcl) is a muscarinic receptor antagonist.IC50 value:Target: muscarinic receptorSolifenacin Hcl (YM905; Vesicare) is a prescription medication used to treat certain bladder problems.

  • CAS Number: 180468-39-7
  • MF: C23H27ClN2O2
  • MW: 398.92600
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: 505.5ºC at 760mmHg
  • Melting Point: 120-122ºC
  • Flash Point: 259.5ºC

BMS-986120

BMS-986120 is an antagonist of the Platelet Protease-Activated Receptor-4 (PAR4), with IC50s of 9.5, 2.1 nM in human and monkey blood, respectively.

  • CAS Number: 1478712-37-6
  • MF: C23H23N5O5S2
  • MW: 513.59
  • Catalog: Protease-Activated Receptor (PAR)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Pramipexole dihydrochloride hydrate

Pramipexole dihydrochloride hydrate is a selective dopamine D2-type receptor agonist, with Kis of 2.2 nM, 3.9 nM, 0.5 nM and 1.3 nM for D2-type receptor, D2, D3 and D4 receptors, respectively. Pramipexole dihydrochloride hydrate can be used for the research of Parkinson's disease (PD) and restless legs syndrome (RLS). Pramipexole dihydrochloride hydrate can cross the blood-brain barrier (BBB)[1][2][3].

  • CAS Number: 191217-81-9
  • MF: C10H21Cl2N3OS
  • MW: 302.264
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: 378ºC at 760 mmHg
  • Melting Point: 290 °C(dec.)
  • Flash Point: 182.4ºC

MFZ 10-7

MFZ 10-7 is a potent mGluR5 antagonist. Intraperitoneal administration of MFZ 10-7 inhibits intravenous cocaine self-administration, cocaine-induced reinstatement of drug-seeking behavior and cocaine-associated cue-induced cocaine-seeking behavior in rats[1]..

  • CAS Number: 1224431-15-5
  • MF: C15H9FN2
  • MW: 236.24400
  • Catalog: mGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

VCP171

VCP171 is a potent adenosine A1 receptor (A1R) positive allosteric modulator (PAM). VCP171 is effective at decreasing excitatory synaptic currents in Lamina II of neuropathic pain model. VCP171 can be used for researching neuropathic pain[1].

  • CAS Number: 1018830-99-3
  • MF: C18H12F3NOS
  • MW: 347.354
  • Catalog: Adenosine Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 507.0±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 260.4±30.1 °C

Remoxipride

(S)-Remoxipride ((-)-Remoxipride) is a selective dopamine D2-receptor antagonist with an IC50 value of 1.57 μM. (S)-Remoxipride can be used for the research of psychotic disorder[1].

  • CAS Number: 80125-14-0
  • MF: C16H23BrN2O3
  • MW: 371.26900
  • Catalog: Dopamine Receptor
  • Density: 1.292
  • Boiling Point: 439.9ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 219.8ºC

ZIMELIDINE DIHYDROCHLORIDE

Zimelidine dihydrochloride is a potent and selective inhibitor of serotonin 5-HT uptake and SERT. Zimelidine dihydrochloride is an antidepressant[1].

  • CAS Number: 60525-15-7
  • MF: C16H18BrClN2
  • MW: 353.68500
  • Catalog: 5-HT Receptor
  • Density: 1.286g/cm3
  • Boiling Point: 412.8ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 203.4ºC

L 888607 Racemate

L 888607 Racemate is a selective prostaglandin D2 receptor subtype 1 (DP1) antagonist, with Kis of 132 nM and 17 nM for DP1 and thromboxane A2 receptor (TP), respectively.

  • CAS Number: 1030017-51-6
  • MF: C19H15ClFNO2S
  • MW: 375.84400
  • Catalog: Prostaglandin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bethanechol chloride

Bethanechol Chloride is a selective muscarinic receptor agonist without any effect on nicotinic receptors.Target: mAChRBethanechol is a parasympathomimetic choline carbamate that selectively stimulates muscarinic receptors without any effect on nicotinic receptors. Unlike acetylcholine, bethanechol is not hydrolyzed by cholinesterase and will therefore have a long duration of action. Oral bethanechol significantly improves contraction pressures and bolus transit in the smooth muscle portion of the esophagus in patients with severe IEM [1]. Bethanechol has potential benefit in the treatment of cerebral palsy [2].

  • CAS Number: 590-63-6
  • MF: C7H17ClN2O2
  • MW: 196.68
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 187-190ºC
  • Flash Point: N/A

JNJ-26070109

A novel, potent, selective orally active CCK-2 receptor antagonist with pKi of 8.49 for hCCK2; displays >1200-fold selectivity over hCCK1 receptor; has oral EC50 of 1.5 and 0.26 uM in conscious rat and dog chronic gastric fistula models of pentagastrin-stimulated acid secretion, respectively; inhibits gastric acid secretion and prevents omeprazole-induced acid rebound in the rats.

  • CAS Number: 844645-08-5
  • MF: C23H17BrF2N4O3S
  • MW: 547.37
  • Catalog: Cholecystokinin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ZINC69391

ZINC69391, a specific Rac1 inhibitor, interferes with Rac1-GEF interaction by masking Trp56 residue on Rac1 surface. ZINC69391 interferes with the interaction of Rac1 with Dock180 and reduces Rac1-GTP levels. ZINC69391 induces apoptosis, and shows antiproliferative and antimetastatic effects[1][2][3].

  • CAS Number: 303094-67-9
  • MF: C14H14F3N5
  • MW: 309.29
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Pitolisant oxalate

Pitolisant oxalate is a potent and selective nonimidazole inverse agonist at the recombinant human histamine H3 receptor (Ki=0.16 nM).

  • CAS Number: 362665-57-4
  • MF: C19H28ClNO5
  • MW: 385.882
  • Catalog: Histamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SB271046

SB 271046 is a potent, selective and orally active 5-HT6 receptor antagonist with a pKi of 8.92-9.09. SB 271046 show >200-fold selective for the 5-HT6 receptor over other receptors, binding sites and ion channels. SB 271046 has anticonvulsant activity[1].

  • CAS Number: 209481-20-9
  • MF: C20H23Cl2N3O3S2
  • MW: 488.45100
  • Catalog: 5-HT Receptor
  • Density: 1.400
  • Boiling Point: 664.3ºC at 760 mmHg
  • Melting Point: 240-241℃ (DEC.)
  • Flash Point: 355.5ºC

LTF4

Leukotriene F4 (LTF4), is a lipid that belongs to the Cysteinyl Leukotriene (CysTL) family[1]. Leukotriene F4 induces bronchoconstriction with an ED50 of 16 μg/kg[2]. The precursor of LTF4 is Leukotriene E4 (LTE4), which isformed from the action of a glutamyl transferase[1].

  • CAS Number: 83851-42-7
  • MF: C28H44N2O8S
  • MW: 568.723
  • Catalog: Leukotriene Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 872.8±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 481.6±34.3 °C

H4R antagonist 1

H4R antagonist 1 is a potent and highly selective histamine H4 receptor (H4R) antagonist with an IC50 of 27 nM. H4R antagonist 1 does not show any noticeable binding affinity to other subtypes of histamine receptors, H1R, H2R, and H3R[1].

  • CAS Number: 1429375-54-1
  • MF: C11H11BrN8
  • MW: 335.16
  • Catalog: Histamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GSK 2018682

GSK2018682 is an agonist for S1P1 and S1P5 receptor with pEC50s of 7.7 and 7.2, respectively, and has no agonist activity towards human S1P2, S1P3, or S1P4. GSK2018682 is used in the research of multiple sclerosis.

  • CAS Number: 1034688-30-6
  • MF: C22H21ClN4O4
  • MW: 440.88
  • Catalog: LPL Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CCG-63802

CCG-63802 is a reversible inhibitor of regulator of G-protein signaling (RGS) protein; with greatest potency at RGS4.IC50 value:Target: RGSCCG-63802 is selective amongst RGS proteins, with greatest potency at RGS4. CCG-63802 inhibits GTPase accelerating protein activity of RGS4 and blocks its interaction with Gαo. Retains activity under reducing conditions.

  • CAS Number: 620112-78-9
  • MF: C26H18N4O2S
  • MW: 450.51200
  • Catalog: RGS Protein
  • Density: 1.31
  • Boiling Point: 547.9ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 285.1ºC

(S)-Butaprost free acid

(S)-Butaprost (free acid) is a potent and highly selective agonist of EP2 receptor[1].

  • CAS Number: 433219-55-7
  • MF: C23H38O5
  • MW: 394.545
  • Catalog: Prostaglandin Receptor
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 565.7±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 310.0±26.6 °C

Alvameline

Alvameline (Lu25-109) is a partial M1 agonist and M2/M3 antagonist.

  • CAS Number: 120241-31-8
  • MF: C9H15N5
  • MW: 193.24900
  • Catalog: mAChR
  • Density: 1.25g/cm3
  • Boiling Point: 342.1ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 160.7ºC

GR 125487 sulfamate

GR125487 sulfamate is an orally active and selective antagonist of 5-HT4R. GR125487 sulfamate effectively blocks the cognition enhancing effect. GR125487 sulfamate can be used to study memory disorders, gastrointestinal disorders, mood disorders and urinary tract dysfunction[1].

  • CAS Number: 859502-43-5
  • MF: C19H29FN4O8S2
  • MW: 524.58
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BQ-788

BQ-788 is a potent, selective ETB receptor antagonist with IC50 of 1.2 nM for inhibition of ET-1 binding to human Girardi heart cells, poorly inhibiting the binding to ETA receptors in human neuroblastoma cell line SK-N-MC cells with IC50 of 1300 nM.

  • CAS Number: 173326-37-9
  • MF: C34H51N5O7
  • MW: 641.79800
  • Catalog: Endothelin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A