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 >
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Antibody-drug Conjugate >
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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 >
5-HT Receptor AChE Adenosine Kinase Amyloid-β Beta-secretase CaMK CGRP Receptor COMT Dopamine Receptor Dopamine Transporter FAAH GABA Receptor GlyT iGluR Imidazoline Receptor mAChR Melatonin Receptor Monoamine Oxidase nAChR Neurokinin Receptor Opioid Receptor Serotonin Transporter γ-secretase
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5-HT2 agonist-1 free base

5-HT2 agonist-1 (Compound 24) free base is a 5-HT2A & 5-HT2B & 5-HT2C agonist, with IC50s of 10 nM, 8.3, and 1.6 nM respectively. 5-HT2 agonist-1 free base can be used for research of depression, alcoholism, tobacco and cocaine addiction, inflammation, cluster headache, PTSD, seizure disorders and other CNS disorders[1].

  • CAS Number: 2708279-77-8
  • MF: C19H22N2O2
  • MW: 310.39
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Alizapride

Alizapride is a potent antiemetic, acting as a dopamine receptor antagonist. Alizapride also used in human digestive disorders[1][3].

  • CAS Number: 59338-93-1
  • MF: C16H21N5O2
  • MW: 315.37000
  • Catalog: Dopamine Receptor
  • Density: 1.224 g/cm3
  • Boiling Point: 597.6ºC at 760 mmHg
  • Melting Point: 3360°C
  • Flash Point: 315.2ºC

BMS-986121

BMS-986121 is a positive allosteric modulator (PAM) of the μ opioid receptor extracted from patent WO2014107344. BMS-986121 is built on a chemical scaffold representing a new chemotype for μ receptor PAMs[1][2][3].

  • CAS Number: 313671-26-0
  • MF: C15H9Cl2N3O2S
  • MW: 366.22
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tranilast Sodium

Tranilast is an antiallergic agent.Target: Angiotensin ReceptorTranilast has been approved in Japan and South Korea, since 1982, for the treatment of bronchial asthma, with indications for keloids and hypertrophic scar added in 1993. Tranilast is also used to treat asthma, autoimmune diseases, atopic and fibrotic pathologies, and can also inhibit angiogenesis. The antiproliferative properties of tranilast were found that tranilast elicited an inhibitory effect on fibroblast proliferation in vitro and also suppressed collagen production both in vitro and in vivo . Tranilast also reduced the release of chemical mediators from mast cells and suppressed hypersensitivity reactions. [1]Three-week-old C57Bl/10 and mdx mice received tranilast (~300 mg/kg) in their food for 9 weeks, after which fibrosis was assessed through histological analyses, and functional properties of tibialis anterior muscles were assessed in situ and diaphragm muscle strips in vitro. Tranilast administration did not significantly alter the mass of any muscles in control or mdx mice, but it decreased fibrosis in the severely affected diaphragm muscle by 31% compared with untreated mdx mice (P<0.05) [2].

  • CAS Number: 104931-56-8
  • MF: C18H16NNaO5
  • MW: 349.313
  • Catalog: Angiotensin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SB408124

SB408124 is a non-peptide antagonist for OX1 receptor with Ki of 57 nM and 27 nM in both whole cell and membrane, respectively; exhibits 50-fold selectivity over OX2 receptor.IC50 Value: 57 nM(Ki)Target: OX1 Receptorin vitro: SB-408124 binds hypocretin type 1 receptor (HcrtR1) with pKi values of 7.57. Calcium mobilization studies shows that SB-408124 is a functional antagonist of the OX1 receptor with a affinity of approximately 50-fold selectivity over the OX2 receptor. A recent study indicates that pretreatment of primary cultures of rat astrocytes with SB-401824 before Orexin A administration significantly reduced the stimulatory action of Orexin A on both basal and forskolin-acivated cAMP production.in vivo: SB-408124 (30 μg/10 μL, administered intracerebroventricularly) decreases Orexin-A induced water intake in Wistar rats. Intracerebroventricularly administered Orexin-A (30 μg/10 μL) blocks the vasopressin (VP) level increase induced by either histamine or 2.5% NaCl administration, and this blocking effect is moderated by pretreatment with SB-408124. Intracerebroventricular pretreatment with SB-408124 (50 mM, 5 μL/h) prevents Bicuculline (BIC)-induced increases in endogenous glucose production (EGP).

  • CAS Number: 288150-92-5
  • MF: C19H18F2N4O
  • MW: 356.369
  • Catalog: Orexin Receptor (OX Receptor)
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 430.3±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 214.0±28.7 °C

CB1/2 agonist 4

CB1/2 agonist 4 (compound 24) is a full CB1 agonist and CB2 partial agonist with EC50 values of 15.09 nM and 1.16 nM, respectively. CB1/2 agonist 4 (compound 24) has a significant antinociceptive activity, and also can activate cannabinoid and TRPV1 receptor with values of IC50 and EC50 is 0.8 μM and 0.12 μM, respectively[1].

  • CAS Number: 2772949-38-7
  • MF: C27H45NO3
  • MW: 431.65
  • Catalog: Cannabinoid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BML-190

BML-190(IMMA) is a potent and selective CB2 receptor ligand (Ki values are 435 nM and > 2 μM for CB2 and CB1 respectively). IC50 Value: 435 nM(Ki CB2)Target:CB2 receptorin vitro: BML-190 increases the accumulation of cAMP, via forskolin-stimulated mechanism in HEK-293 cells. Alternate studies suggest that BML-190 reduces the toxicity of culture supernatants to SH-SY5Y human neutroblastoma cells. Various research suggests that BML-190 is an essential tool in studying the proliferation of neuroblastoma. BML-190 diminishes LPS-induced NO and IL-6 production in a concentration-dependent manner. BML-190 also inhibits LPS-induced PGE2 production and COX-2 induction. in vivo:

  • CAS Number: 2854-32-2
  • MF: C23H23ClN2O4
  • MW: 426.893
  • Catalog: Cannabinoid Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 586.7±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 308.6±30.1 °C

Eldelumab

Eldelumab (BMS-936557) is a humanised anti-CXCL10 (IP-10) monoclonal antibody (IgG1 type). Eldelumab selectively binds to CXCL10 and blocks CXCL10-induced calcium flux and cell migration. Eldelumab can be used in studies of autoimmune and auto-inflammatory diseases such as rheumatoid arthritis, ulcerative colitis and crohn's disease[1][2].

  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BX 471

BX471 (ZK-811752) is a potent and selective non-peptide CCR1 antagonist with a Ki of 1 nM, and exhibits 250-fold selectivity for CCR1 over CCR2, CCR5 and CXCR4.

  • CAS Number: 217645-70-0
  • MF: C21H24ClFN4O3
  • MW: 434.892
  • Catalog: CCR
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 593.5±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 312.8±30.1 °C

Proglumide hemicalcium

Proglumide hemicalcium is a nonpeptide and orally active cholecystokinin (CCK)-A/B receptors antagonist. Proglumide hemicalcium selective blocks CCK’s effects in the central nervous system (CNS). Proglumide hemicalcium has ability to inhibit gastric secretion and to protect the gastroduodenal mucosa. Proglumide hemicalcium also has antiepileptic and antioxidant activities[1][2][3][4][5].

  • CAS Number: 85068-56-0
  • MF: C18H26N2O4.1/2Ca
  • MW: 706.88200
  • Catalog: Cholecystokinin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Mapenterol-d6 hydrochloride

Mapenterol-d6 hydrochloride is the deuterium labeled Mapenterol hydrochloride. Mapenterol hydrochloride is a type of β2-adrenoceptor agonist[1][2].

  • CAS Number: 1246816-02-3
  • MF: C14H15D6Cl2F3N2O
  • MW: 330.81
  • Catalog: Adrenergic Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tiodazosin

Tiodazosin is a potent competitive postsynaptic alpha adrenergic receptor antagonist.

  • CAS Number: 66969-81-1
  • MF: C18H21N7O4S
  • MW: 431.46900
  • Catalog: Adrenergic Receptor
  • Density: 1.5g/cm3
  • Boiling Point: 690.2ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 371.2ºC

CGS 15435

CGS 15435, a potent thromboxane (TxA2) synthetase inhibitor with an IC50 of 1 nM, has a selectivity for Tx synthetase 100000-fold greater than that for cyclooxygenase, PGI2 synthetase and lipoxygenase enzymes.

  • CAS Number: 95853-92-2
  • MF: C20H21ClN2O2
  • MW: 356.85
  • Catalog: Prostaglandin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Naxagolide

Naxagolide ((+)-PHNO; Dopazinol) is a potent dopamine D2 (Dopamine Receptor) agonist. Naxagolide has the potential for the research of parkinson's disease (PD)[1][2].

  • CAS Number: 88058-88-2
  • MF: C15H21NO2
  • MW: 247.333
  • Catalog: Dopamine Receptor
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 391.7±42.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 190.7±27.9 °C

Val9-Oxytocin

Val9-Oxytocin is a full antagonist of vasopressin (V1a) receptor. Val9-Oxytocin is an analog of Oxytocin (HY-17571A) in which changing Gly9 to Val9[1].

  • CAS Number: 1021701-88-1
  • MF: C46H72N12O12S2
  • MW: 1049.27
  • Catalog: Vasopressin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

L-159282

L-159282 is a highly potent, orally active, nonpeptide angiotensin II receptor antagonist, with anti-hypertensive activity.

  • CAS Number: 157263-00-8
  • MF: C30H28N4O3S
  • MW: 524.63300
  • Catalog: Angiotensin Receptor
  • Density: 1.27g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

[DGlp1,DPhe2,DTrp3,6]-LH-RH

[D-Glp1,D-Phe2,D-Trp3,6]-LH-RH is a Luteinizing-hormone-releasing hormone (LHRH) analogue. [D-Glp1,D-Phe2,D-Trp3,6]-LH-RH acts as a GnRH receptor antagonist[1].

  • CAS Number: 68059-94-9
  • MF: C67H84N16O13
  • MW: 1321.48000
  • Catalog: GNRH Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ST-1006

ST-1006 is a potent histamine H4 receptor agonist with a pKi value of 7.94. ST-1006 has anti-inflammatory effect[1][2].

  • CAS Number: 1196994-11-2
  • MF: C16H20Cl2N6
  • MW: 367.28
  • Catalog: Histamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tiapride

Tiapride, an atypical neuroleptic agent, is a selective dopamine D2-receptor antagonist with little propensity for causing catalepsy and sedation. The IC50 values of Tiapride are 1440, 45.8, >100, and 11.7 μM for D1; D2; D3; D4, respectively[1].

  • CAS Number: 51012-32-9
  • MF: C15H24N2O4S
  • MW: 328.42700
  • Catalog: Dopamine Receptor
  • Density: 1.15 g/cm3
  • Boiling Point: 498.1ºC at 760 mmHg
  • Melting Point: 120ºC
  • Flash Point: 255.1ºC

AZD1981

AZD1981 is a potent and selective CRTh2 antagonist; displaces radio-labelled PGD2 from human recombinant DP2 with high potency (pIC50 = 8.4).IC50 value:Target: GPR44 antagonistin vitro: AZD1981 produced a concentration-dependent displacement of the [3H]PGD2-specific binding with a mean pIC50 of 8.4 ± 0.1 (n = 25, geometric mean IC50 of 4 nM). AZD1981 had no significant affinity towards recombinant human DP1 receptors with only a mean 27% (range 14–50%; n = 4) displacement of [3H]PGD2-specific binding observed at the highest concentration tested (10 μM). Compared with the binding potency for DP2, AZD1981 showed 10-fold selectivity over rat aldose reductase and 1700-fold selectivity over rat steroid 5α-reductase.In eosinophils, a single concentration of 1 μM, AZD1981 caused a large (20-fold) rightward parallel shift in the 15R-methyl PGD2 E/[A] curve with no evidence of a decrease in the maximal response. The effect of AZD1981 was therefore investigated using a single sub-maximal concentration of agonist (1 μM). AZD1981 produced a concentration-dependent inhibition of eosinophil migration with a pIC50 value of 7.6 ± 0.1 (n = 4) [1].in vivo: Using the previously described guinea pig hind limb model , 10 nM AZD1981 significantly inhibited DK-PGD2-induced eosinophil mobilization by approximately 50%, and the response was completely inhibited with 100 nM AZD1981 [1]. in vivo: AZD1981 exhibited good cross-species binding activity against mouse, rat, guinea pig, rabbit and dog DP2 . Evaluation in mouse, rat or rabbit cell systems was not possible as they did not respond to DP2 agonists. Agonist responses were seen in guinea pig and dog, and AZD1981 blocked DP2 -mediated eosinophil shape change. Such responses were more robust in the guinea pig, where AZD1981 also blocked DP2 -dependent eosinophil emigration from bone marrow [1]. There was no beneficial clinical effect of AZD1981, at a dose of 1000 mg twice daily for 4 weeks, in patients with moderate to severe COPD. AZD1981 was well tolerated and no safety concerns were identified [3].

  • CAS Number: 802904-66-1
  • MF: C19H17ClN2O3S
  • MW: 388.86800
  • Catalog: Prostaglandin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MRTX849 acid

MRTX849 acid, a derivative of MRTX849, can be used in the synthesis of PROTAC LC-2 (HY-137516). LC-2 is a potent and first-in-class PROTAC capable of degrading endogenous KRAS G12C (DC50s between 0.25 and 0.76 μM)[1][2].

  • CAS Number: 2561529-96-0
  • MF: C34H37ClFN7O4
  • MW: 662.15
  • Catalog: Ras
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

USL311

USL311 is a selective CXCR4 antagonist, with anti-tumor activity[1].

  • CAS Number: 1373268-67-7
  • MF: C24H34N6O
  • MW: 422.57
  • Catalog: CXCR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Buspirone

Buspirone is an orally active 5-HT1A receptor agonist. Buspirone is a potent anticancer agent. Buspirone shows antiproliferative activity. Buspirone can be used for anxiety, depression and cancer research[1][2].

  • CAS Number: 36505-84-7
  • MF: C21H31N5O2
  • MW: 385.50300
  • Catalog: 5-HT Receptor
  • Density: 1.24g/cm3
  • Boiling Point: 613.9ºC at 760 mmHg
  • Melting Point: 41678ºC
  • Flash Point: 325.1ºC

Aganepag

Aganepag is a potent Prostanoid EP2 receptor agonist, with an EC50 of 0.19 nM, and shows no activity at EP4 receptor. Aganepag can be used in the research of wound healing, scar reduction, scar prevention and wrinkle treatment and prevention.

  • CAS Number: 910562-18-4
  • MF: C24H31NO4S
  • MW: 429.57200
  • Catalog: Prostaglandin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CXCR7 antagonist-1

CXCR7 antagonist-1 is an inhibitor of the binding of the SDF-1 chemokine (CXCL12 chemokine) or I-TAC (CXCL11) to the chemokine receptor CXCR. CXCR7 antagonist-1 prevents tumor cell proliferation, tumor formation, inflammatory diseases, and many other diseases (extracted from patent WO2014085490A1, compound 1.128)[1].

  • CAS Number: 1613021-99-0
  • MF: C21H19FN6O
  • MW: 390.41
  • Catalog: CXCR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(±)-Muscarine chloride

(±)-Muscarine chloride is the racemate of Muscarine chloride. Muscarine is a prototype muscarinic acetylcholine receptor agonist[1][2].

  • CAS Number: 2936-25-6
  • MF: C9H20ClNO2
  • MW: 209.71400
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 180-181ºC
  • Flash Point: N/A

Thioperamide (maleate)

Thioperamide maleate (MR-12842 maleate) is a potent, orally available, brain penetrant and selective H3 receptor antagonist with a Ki of 4.3 nM for inhibition of [3H]histamine release. Thioperamide maleate inhibits [3H]histamine synthesis with a Ki of 31 nM[1].

  • CAS Number: 148440-81-7
  • MF: C19H28N4O4S
  • MW: 408.515
  • Catalog: Histamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Fasiglifam(TAK-875)

Fasiglifam (TAK-875) hemihydrate is a potent, selective and orally active GPR40 agonist with EC50 of 72 nM. Fasiglifam enhances glucose-dependent insulin secretion and improves hyperglycemia in type 2 diabetic rats. Fasiglifam can induce liver injury[1][2][3][4].

  • CAS Number: 1374598-80-7
  • MF: C29H33O7.5S
  • MW: 533.63
  • Catalog: GPR40
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Molindone-d8

Molindone-d8 is the deuterium labeled Molindone. Molindone hydrochloride (EN-1733A) is a therapeutic antipsychotic, used in the treatment of schizophrenia, works by blocking the effects of dopamine in the brain, leading to diminished psychoses[1][2].

  • CAS Number: 1189805-13-7
  • MF: C16H16D8N2O2
  • MW: 284.42300
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SNT-207707

SNT-207707 is a selective, potent and orally active melanocortin MC-4 receptor antagonist with an IC50 of 8 nM (binding) and 5 nM (function) on the MC-4 receptor.

  • CAS Number: 1064662-40-3
  • MF: C32H44ClN5O
  • MW: 550.17800
  • Catalog: Cancer
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A