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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ZK 756326

ZK756326 dihydrochloride is a nonpeptide chemokine receptor agonist for the CC chemokine receptor CCR8.

  • CAS Number: 1780259-94-0
  • MF: C21H30Cl2N2O3
  • MW: 429.38
  • Catalog: CCR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PF-00446687

PF-00446687 is a potent, selective melanocortin-4 receptor (MC4R) agonist with EC50 of 12 ± 1 nM[1]. Pf-446687 is brain penetrant[2].

  • CAS Number: 862281-92-3
  • MF: C28H36F2N2O2
  • MW: 470.59400
  • Catalog: Endocrinology
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Kelatorphan

Kelatorphan is a full inhibitor of enkephalin degrading enzymes.

  • CAS Number: 92175-57-0
  • MF: C14H18N2O5
  • MW: 294.30300
  • Catalog: Opioid Receptor
  • Density: 1.301g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PYR-PHE-PHE-GLY-LEU-MET-NH2

[Glp6] Substance P (6-11) is an analogue of substance P (6-11). Substance P (6-11) stimulates [3H]-inositol monophosphate ([3H]-IP1) formation in rat urinary bladder by acting on the 'septide-sensitive' tachykinin receptors[1][2].

  • CAS Number: 61123-13-5
  • MF: C36H49N7O7S
  • MW: 723.88200
  • Catalog: Neurokinin Receptor
  • Density: 1.247g/cm3
  • Boiling Point: 1195.9ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 677ºC

Zamifenacin

Zamifenacin (UK-76654) is a potent gut-selective muscarinic M3 receptor antagonist. Zamifenacin significantly reduces colonic motility in irritable bowel syndrome[1].

  • CAS Number: 127308-82-1
  • MF: C27H29NO3
  • MW: 415.52400
  • Catalog: mAChR
  • Density: 1.2g/cm3
  • Boiling Point: 532.5ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 145.6ºC

CCX140

CCX140 is a potent CCR2 antagonist.

  • CAS Number: 1100318-47-5
  • MF: C20H13ClF3N5O3S
  • MW: 495.862
  • Catalog: CCR
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 714.8±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 386.1±35.7 °C

NALTRIBEN MESYLATE

Naltriben is a selective δ2-opioid receptor antagonist and TRPM7 activator. Naltriben enhances glioblastoma cell migration and invasion. Naltriben can be used in research into neurological diseases and cancer[1][2].

  • CAS Number: 111555-58-9
  • MF: C26H25NO4
  • MW: 415.48
  • Catalog: Opioid Receptor
  • Density: 1.5 g/cm3
  • Boiling Point: 605.3ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 319.9ºC

Tazomeline

Tazomeline is a selective M1 muscarinic receptor agonist. Tazomeline inhibits twitch height in rabbit vas deferens(IC50= 0.001 nM). Tazomeline can be used for research of neuropsychiatric disorders[1].

  • CAS Number: 131987-54-7
  • MF: C14H23N3S2
  • MW: 297.48300
  • Catalog: mAChR
  • Density: 1.15g/cm3
  • Boiling Point: 407.8ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 200.4ºC

Butoxamin

Butaxamine (Butoxamin) is a potent, selective and orally active β2-adrenoceptor antagonist. Butaxamine shows antiosteoporotic activity[1].

  • CAS Number: 2922-20-5
  • MF: C15H25NO3
  • MW: 267.36400
  • Catalog: Adrenergic Receptor
  • Density: 1.027g/cm3
  • Boiling Point: 391ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 190.3ºC

MK-447

MK-447 is a free radical scavenger, also a nonsteroidal antiinflammatory agent, and enhances the formation of the endoperoxide, PGH2, and other prostaglandins.

  • CAS Number: 58456-91-0
  • MF: C11H16INO
  • MW: 305.15500
  • Catalog: Prostaglandin Receptor
  • Density: 1.552g/cm3
  • Boiling Point: 306.9ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 139.4ºC

TC-MCH 7c

TC-MCH 7c, a phenylpyridone derivative, is an orally available, selective and brain-penetrable MCH1R antagonist with an IC50 of 5.6 nM for hMCH1R[1]. TC-MCH 7c has Kis of 3.4 nM and 3.0 nM of human and mouse MCH1R, respectively[2].

  • CAS Number: 864756-35-4
  • MF: C24H25FN2O3
  • MW: 408.46500
  • Catalog: MCHR1 (GPR24)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ecopipam hydrochloride

Ecopipam (SCH 39166) hydrochloride is a potent, selective and orally active antagonist of dopamine D1/D5 receptor, with Kis of 1.2 nM and 2.0 nM, respectively. Ecopipam hydrochloride shows more than 40-flod selectivity over D2, D4, 5-HT, and α2a receptor (Ki=0.98, 5.52, 0.08, and 0.73 μM, respectively). Ecopipam hydrochloride can be used for the research of schizophrenia, cocaine addition, and obesity[1][3].

  • CAS Number: 190133-94-9
  • MF: C19H21Cl2NO
  • MW: 350.28200
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BMS-986166

BMS-986166 (BMS986166) is a potent, selective S1P receptor modulator for the treatment of ulcerative colitis.

  • CAS Number: 1883345-06-9
  • MF: C25H33NO2
  • MW: 379.544
  • Catalog: LPL Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ACT-672125

ACT-672125 is a potent CXCR3 antagonist with IC50 value of 239 nM in human blood. ACT-672125 has activity for hERG with IC50 value of 18μM. ACT-672125 can be used for the research of autoimmune diseases[1].

  • CAS Number: 1449367-94-5
  • MF: C25H25F3N10O2S
  • MW: 586.59
  • Catalog: CXCR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

[D-Trp11]-Neurotensin

[D-Trp11]-Neurotensin, an analogue of Neurotensin (NT), is a selective antagonist of NT in perfused rat hearts but behaves as a full agonist in guinea pig atria and rat stomach strips. [D-Trp11]-Neurotensin can inhibit NT-induced hypotension[1][2].

  • CAS Number: 73634-68-1
  • MF: C80H122N22O19
  • MW: 1695.96
  • Catalog: Neurotensin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Melatonin receptor agonist 1

Melatonin receptor agonist 1 (compound 20c) is a potent melatonin receptor (MT) agonist, with Ki values of 108 nM (MT2) and 1140 nM (MT1)[1].

  • CAS Number: 2411150-76-8
  • MF: C15H19N3O2
  • MW: 273.33
  • Catalog: Melatonin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Pan KRas-IN-1

Pan KRas-IN-1 is a pan KRas inhibitor, can be used for drug resistance in cancer developed with KRas G12C inhibitors[1].

  • CAS Number: 2791263-84-6
  • MF: C33H36F3N5O3
  • MW: 607.67
  • Catalog: Ras
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Chamazulene

Chamazulene, a natural compound, is an antioxidant-type inhibitor of leukotriene B4 formation[1].

  • CAS Number: 529-05-5
  • MF: C14H16
  • MW: 184.277
  • Catalog: Leukotriene Receptor
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 299.1±20.0 °C at 760 mmHg
  • Melting Point: <25℃
  • Flash Point: 137.4±12.5 °C

SB 271046 (Hydrochloride)

SB271046 Hcl is a potent, selective and orally active 5-HT6 receptor antagonist with pKi of 8.9.IC50 Value: 8.9(pKi)Target: 5-HT6 Receptorin vitro: SB 271046 hydrochloride is a sulfonamidal benzothiophene derivative that has been shown to act as a selective 5-HT6 antagonist with pKi values of 9.02-8.92, 6.55, 6.35, 6.27, 6.05, 5.95, 5.76, 5.73, 5.62, 5.55, 5.41, 5.39, 5.27 and < 4.99 for 5-HT6, 5-HT1D, 5-HT1A, D3, 5-HT1B, 5-HT1F, α1B, 5-HT2C, 5-HT2A, D2, 5-HT2B, 5-HT7, 5-HT4 and 5-HT1E respectively, and is > 200-fold selective over 55 other receptors, enzymes and ion channels.in vivo: SB-271046 is moderately brain penetrant (10%), subject to low blood clearance (7.7 mL/min/kg) with a good half-life in rats (4.8 hours), and has excellent oral bioavailability (>80%). SB-271046 produces 3-fold and 2-fold increases in extracellular glutamate levels in both frontal cortex and dorsal hippocampus of rats, respectively, which may be used for the treatment of cognitive and memory dysfunction. SB-271046 (20 mg/kg, orally gavage) 30 min prior to training Wistar rats, is found to reverse significantly the amnesia produced by administering scopolamine (0.8 mg/kg, i.p.) in the 6 hours post-training period. SB-271046 progressively and significantly decreases platform swim angle and escape latencies over the five sequential trials on four consecutive daily sessions compared to vehicle-treated controls in aged rats. SB-271046 also improves task recall as measured by significant increases in the searching of the target quadrant on post-training days 1 and 3. SB-271046 (10 mg/kg, s.c.) produces a significant, tetrodotoxin-dependent, increase in extracellular levels of both glutamate and aspartate within the frontal cortex of rats, reaching maximum values of 375.4% and 215.3% of preinjection values, respectively.

  • CAS Number: 209481-24-3
  • MF: C20H23Cl2N3O3S2
  • MW: 488.45
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

R 138727

R-138727, the thiol-containing active metabolite of Prasugrel, is an irreversible platelet P2Y12 receptor inhibitor. R-138727 inhibits ADP-induced platelet aggregation[1].

  • CAS Number: 204204-73-9
  • MF: C18H20FNO3S
  • MW: 349.42
  • Catalog: P2Y Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 513.4±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 264.3±30.1 °C

CGP 71683 HCl

CGP71683 hydrochloride is a competitive neuropeptide Y5 receptor antagonist with a Ki of 1.3 nM, and shows no obvious activity at Y1 receptor (Ki, >4000 nM) and Y2 receptor (Ki, 200 nM) in cell membranes.

  • CAS Number: 192322-50-2
  • MF: C26H30ClN5O2S
  • MW: 512.06700
  • Catalog: Neuropeptide Y Receptor
  • Density: N/A
  • Boiling Point: 747.2ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 405.7ºC

Cyclobuxine D

Cyclobuxine D is a steroidal alkaloid extracted from Buxus microphylla. Cyclobuxine D has a significant bradycardic effect in the rat heart and an inhibitory action on acetylcholine and Ba++−induced contraction of the longitudinal muscle isolated from the rabbit jejunum[1][2].

  • CAS Number: 2241-90-9
  • MF: C25H42N2O
  • MW: 386.61400
  • Catalog: mAChR
  • Density: 1.08g/cm3
  • Boiling Point: 494.2ºC at 760mmHg
  • Melting Point: 236-238ºC
  • Flash Point: 53.5ºC

Isoferulic acid

3-Hydroxy-4-methoxycinnamic acid (Isoferulic acid) is a cinnamic acid derivative that has antidiabetic activity. 3-Hydroxy-4-methoxycinnamic acid binds to and activates α1-adrenergic receptors (IC50=1.4 µM) to enhance secretion of β-endorphin (EC50=52.2 nM) and increase glucose use.

  • CAS Number: 537-73-5
  • MF: C10H10O4
  • MW: 194.184
  • Catalog: Adrenergic Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 410.2±35.0 °C at 760 mmHg
  • Melting Point: 230 °C (dec.)(lit.)
  • Flash Point: 167.6±19.4 °C

4-Thiouridine 5′-triphosphate tetralithium

4-Thiouridine 5′-triphosphate (4-Thio-UTP) tetralithium is a potent P2Y2 and P2Y4 receptor agonist, with EC50s of 35 and 350 nM for hP2Y2 and hP2Y4, respectively. 4-Thiouridine 5′-triphosphate tetralithium can be used in the study of crosslinking experiments, labeling of transcriptional complex[1][2].

  • CAS Number: 20188-72-1
  • MF: C9H11Li4N2O14P3S
  • MW: 523.94
  • Catalog: P2Y Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Doxazosin

Doxazosin(UK 33274) is a quinazoline-derivative that selectively antagonizes postsynaptic α1-adrenergic receptors.Target: Adrenergic ReceptorDoxazosin is a long-lasting inhibitor of α1-adrenoceptors that is widely used to treat benign prostatic hyperplasia and lower urinary tract symptoms [1]. doxazosin may have a direct inhibitory effect on cholesterol synthesis independent of the LDL receptor. The inhibition of cholesterol synthesis by doxazosin may cause cells to compensate by upregulating the LDL receptor, thereby increasing the importation of lipoprotein cholesterol and reducing LDL cholesterol in the medium [2]. Doxazosin monotherapy was effective in eight of 12 patients (66.7%), and combined therapy with a beta-blocker was effective in 11 of 12 patients (91.7%). The mean pulse rate remained constant throughout therapy. Adverse reactions were minor and transient and occurred in only three patients. Urinary and plasma catecholamine levels tended to decrease or remained unchanged during doxazosin therapy [3].Clinical indications: Hypertension; Prostate hyperplasiaFDA Approved Date: February 22, 2005Toxicity: Symptoms of overdose include hypotension

  • CAS Number: 74191-85-8
  • MF: C23H25N5O5
  • MW: 451.48
  • Catalog: Adrenergic Receptor
  • Density: 1.371 g/cm3
  • Boiling Point: 718ºC at 760 mmHg
  • Melting Point: 289-290°C
  • Flash Point: 388ºC

Ambutonium bromide

Ambutonium bromide is an acetylcholine antagonist.

  • CAS Number: 115-51-5
  • MF: C20H27BrN2O
  • MW: 391.34500
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SX-517

A potent, specific, noncompetitive dual CXCR1 and CXCR2 antagonist with IC50 of 38 nM (vs. CXCL1) and 36 nM (vs. CXCL8), respectively; inhibits CXCL1-induced Ca(2+) flux in human PMNs but has no effect on the Ca(2+) flux induced by C5a, fMLF, or PAF; antagonizes CXCL8-induced [(35)S]GTPγS binding (IC50=60 nM) and ERK1/2 phosphorylation in recombinant HEK293 cells expressed CXCR2; significantly inhibits inflammation in an in vivo murine model (0.2 mg/kg iv).

  • CAS Number: 1240494-13-6
  • MF: C19H16BFN2O3S
  • MW: 382.216
  • Catalog: CXCR
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GPR120 modulator 1

GPR120 modulator 1 is useful for modulating G protein-coupled receptor 120 (GPR120).IC50 value:Target: GPR120

  • CAS Number: 1050506-75-6
  • MF: C19H16ClNO4S
  • MW: 389.85300
  • Catalog: GPR120
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Betahistine Mesylate

Betahistine mesylate is an orally active histamine H1 receptor agonist and a H3 receptor antagonist[1]. Betahistine mesylate is used for the study of rheumatoid arthritis (RA)[3].

  • CAS Number: 54856-23-4
  • MF: C10H20N2O6S2
  • MW: 328.406
  • Catalog: Histamine Receptor
  • Density: N/A
  • Boiling Point: 210.9ºC at 760 mmHg
  • Melting Point: 112°C
  • Flash Point: 96.7ºC

Onvitrelin ucalontide

Onvitrelin ucalontide ([Phor18-LHRH (338613)]) is an analogue of luteinizing hormone releasing hormone (LHRH) with antineoplastic activity. Onvitrelin ucalontide is a peptide with sequences of KFAKFAKKFAKFAKKFAKQHWSYGLRPG. Onvitrelin ucalontide effectively inhibits breast cancer, ovarian cancer and prostate cancer xenografts in mouse model[1][2].

  • CAS Number: 1174415-90-7
  • MF: C163H243N43O32
  • MW: 3316.94
  • Catalog: GNRH Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A