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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Zagociguat

Zagociguat is the stimulator of soluble guanylate cyclase. Zagociguat increases nitric oxide (NO) signaling leading to an increase in cyclic guanosine monophosphate production. Zagociguat has the potential for the research of noncentral nervous system (CNS) disorders[1].

  • CAS Number: 2201048-82-8
  • MF: C16H10F4N6
  • MW: 362.28
  • Catalog: Guanylate Cyclase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Lofexidine-d4 hydrochloride

Lofexidine-d4 hydrochloride (Baq-168-d4) is the deuterium labeled Lofexidine hydrochloride. Lofexidine hydrochloride is a selective α2-receptor agonist, commonly used to alleviate the physical symptoms of heroin and other types of opioid withdrawal[1][2].

  • CAS Number: 1206845-57-9
  • MF: C11H9D4Cl3N2O
  • MW: 299.62
  • Catalog: Adrenergic Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HS 014 TFA

HS014 is a potent and selective melanocortin-4 (MC4) receptor antagonist, with Kis of 3.16, 108, 54.4 and 694 nM for human MC4, MC1, MC3 and MC5 receptors, respectively. HS014 modulates the behavioral effects of morphine in mice. HS014 increases food intake in free-feeding rats[1][2][3].

  • CAS Number: 207678-81-7
  • MF: C71H94N20O17S2
  • MW: 1563.760
  • Catalog: Neurological Disease
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Etilevodopa hydrochloride

Etilevodopa (L-Dopa ethyl ester) hydrochloride, an ethyl-ester prodrug of Levodopa, is rapidly hydrolyzed to Levodopa and ethanol by nonspecific esterases in the gastrointestinal tract. Etilevodopa hydrochloride is used for the treatment of Parkinson disease (PD). Levodopa is the direct precursor of dopamine and is a suitable prodrug as it facilitates CNS penetration and delivers dopamine[1][2][3].

  • CAS Number: 39740-30-2
  • MF: C11H16ClNO4
  • MW: 261.70200
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BW 373U86

BW373U86 (SNC86) is a δ-opioid receptor agonist with an IC50 of 1.49 nM. BW373U86 shows antidepressant-like effects[1].

  • CAS Number: 155836-50-3
  • MF: C27H37N3O2
  • MW: 435.60
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BAR501

BAR501 is a potent and selective agonist of GPBAR1 with an EC50 of 1 μM.

  • CAS Number: 1632118-69-4
  • MF: C26H46O3
  • MW: 406.64
  • Catalog: GPCR19
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Palonosetron-d3 hydrochloride

Palonosetron-d3 hydrochloride is the deuterium labeled Palonosetron hydrochloride. Palonosetron hydrochloride is a 5-HT3 antagonist used in the prevention and treatment of chemotherapy-induced nausea and vomiting (CINV)[1][2].

  • CAS Number: 1246816-81-8
  • MF: C19H22D3ClN2O
  • MW: 335.89
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

LY 334370

LY334370 is a selective 5-HT1F receptor agonist with a Ki of 1.6 nM.

  • CAS Number: 182563-08-2
  • MF: C21H22FN3O
  • MW: 351.42
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: 504.1ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 258.7ºC

BIBN-99

BIBN-99 is a selective, BBB-penetrable and competitive muscarinic M2 receptor antagonist. BIBN-99 improves cognitive performancein rats with traumatic brain injury[1][2].

  • CAS Number: 145301-48-0
  • MF: C31H42ClN5O3
  • MW: 568.15000
  • Catalog: mAChR
  • Density: 1.172g/cm3
  • Boiling Point: 709.8ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 383.1ºC

12S-HHTrE

12S-HHT (12(S)-HHTrE) is an enzymatic product of prostaglandin H2 (PGH2) derived from cyclooxygenase (COX)-mediated arachidonic acid metabolism. 12S-HHT is an endogenous ligand for BLT2 that fully activates BLT2 in vivo. 12S-HHT suppresses UV-induced IL-6 synthesis in keratinocytes, exerting an anti-inflammatory activity[1][2].

  • CAS Number: 54397-84-1
  • MF: C17H28O3
  • MW: 280.402
  • Catalog: Leukotriene Receptor
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 451.8±45.0 °C at 760 mmHg
  • Melting Point: 151.79 (Mean or Weighted MP)ºC
  • Flash Point: 241.1±25.2 °C

Diprophylline

Dyphylline acts as an adenosine receptor antagonist and phosphodiesterase inhibitor, which is used in the treatment of respiratory disorders.Target: Adenosine Receptor; PDEDyphylline (trade names Dilor, Lufyllin), also known as diprophylline, is a xanthine derivative with bronchodilator and vasodilator effects. It is used in the treatment of respiratory disorders like asthma, cardiac dyspnea, and bronchitis. It acts as an adenosine receptor antagonist and phosphodiesterase inhibitor.

  • CAS Number: 479-18-5
  • MF: C10H14N4O4
  • MW: 254.243
  • Catalog: Adenosine Receptor
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 589.6±60.0 °C at 760 mmHg
  • Melting Point: 161-162 °C(lit.)
  • Flash Point: 310.4±32.9 °C

8-Hydroxy-DPAT hydrobromide

8-Hydroxy-DPAT hydrobromide (8-OH-DPAT hydrobromide) is a potent and selective 5-HT1A agonist with a pIC50 of 8.19. 8-Hydroxy-DPAT hydrobromide has selectivity of almost 1000 fold for a subtype of the 5-HT1 binding site[1].

  • CAS Number: 76135-31-4
  • MF: C16H26BrNO
  • MW: 328.28800
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MK-6892

MK-6892 is a potent, selective, and full agonist for the high affinity nicotinic acid (NA) receptor GPR109A. Ki and GTPγS EC50 of MK-6892 on the Human GPR109A is 4 nM and 16 nM, respectively.

  • CAS Number: 917910-45-3
  • MF: C19H22N4O5
  • MW: 386.40200
  • Catalog: GPR109A
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Rupatadine

Rupatadine (UR-12592) is a potent dual PAF/H1 antagonist with Ki of 0.55/0.1 uM(rabbit platelet membranes/guinea pig cerebellum membranes).IC50 value:Target: PAF/H1 antagonistin vitro: Rupatadine competitively inhibited histamine-induced guinea pig ileum contraction (pA2 = 9.29 +/- 0.06) without affecting contraction induced by ACh, serotonin or leukotriene D4 (LTD4). It also competitively inhibited PAF-induced platelet aggregation in washed rabbit platelets (WRP) (pA2 = 6.68 +/- 0.08) and in human platelet-rich plasma (HPRP) (IC50 = 0.68 microM), while not affecting ADP- or arachidonic acid-induced platelet aggregation [1]. The IC50 for rupatadine in A23187, concanavalin A and anti-IgE induced histamine release was 0.7+/-0.4 microM, 3.2+/-0.7 microM and 1.5+/-0.4 microM, respectively whereas for loratadine the IC50 was 2.1+/-0.9 microM, 4.0+/-1.3 M and 1.7+/-0.5 microM. SR-27417A exhibited no inhibitory effect [2].in vivo: Rupatadine blocked histamine- and PAF-induced effects in vivo, such as hypotension in rats (ID50 = 1.4 and 0.44 mg/kg i.v., respectively) and bronchoconstriction in guinea pigs (ID50 = 113 and 9.6 micrograms/kg i.v.). Moreover, it potently inhibited PAF-induced mortality in mice (ID50 = 0.31 and 3.0 mg/kg i.v. and p.o., respectively) and endotoxin-induced mortality in mice and rats (ID50 = 1.6 and 0.66 mg/kg i.v.) [1]. rupatadine treatment improved the declined lung function and significantly decreased animal death. Moreover, rupatadine was able not only to attenuate silica-induced silicosis but also to produce a superior therapeutic efficacy compared to pirfenidone, histamine H1 antagonist loratadine, or PAF antagonist CV-3988 [3].

  • CAS Number: 158876-82-5
  • MF: C26H26ClN3
  • MW: 415.958
  • Catalog: Autophagy
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 586.4±50.0 °C at 760 mmHg
  • Melting Point: 58-61ºC
  • Flash Point: 308.4±30.1 °C

Zicronapine

Zicronapine is an antipsychotic medication with a strong pro-cognitive effect in animal models and the potential to treat a number of neurological and psychiatric diseases. Zicronapine has potent antagonistic effects at dopamine D1/D2, and serotonin 5-HT2A receptors.

  • CAS Number: 170381-16-5
  • MF: C22H27ClN2
  • MW: 354.91600
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Dihydrexidine

Dihydrexidine (DAR-100) is a high potent, selective and full efficacy D1 dopamine receptor agonist with an IC50 of 10 nM, and displays some affinity for the D2 receptor. Dihydrexidine (DAR-100) exhibits potent antiparkinsonian activity[1][2][3].

  • CAS Number: 123039-93-0
  • MF: C17H17NO2
  • MW: 303.78300
  • Catalog: Dopamine Receptor
  • Density: 1.267g/cm3
  • Boiling Point: 488.3ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 190.5ºC

Zafirlukast

Zafirlukast is a potent orally active leukotriene D4 (LTD4) receptor antagonist.

  • CAS Number: 107753-78-6
  • MF: C31H33N3O6S
  • MW: 575.675
  • Catalog: Leukotriene Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: 139°C
  • Flash Point: N/A

Phentolamine mesilate

Phentolamine mesylate is a competitive, reversible α-adrenoceptor antagonist with an IC50 between 5 and 30 nM.

  • CAS Number: 65-28-1
  • MF: C18H23N3O4S
  • MW: 377.458
  • Catalog: Adrenergic Receptor
  • Density: N/A
  • Boiling Point: 551ºC at 760 mmHg
  • Melting Point: 180-182 °C(lit.)
  • Flash Point: 287ºC

SB 221284

SB 221284 is a selective 5-HT2C/2B receptor antagonist with pKi values are 6.4, 7.9 and 8.6 for 5-HT2A, 5-HT2B and 5-HT2C receptors, respectively. SB 221284 can be used for the research of neurological disease[1].

  • CAS Number: 196965-14-7
  • MF: C16H14F3N3OS
  • MW: 353.36200
  • Catalog: 5-HT Receptor
  • Density: 1.43g/cm3
  • Boiling Point: 536.2ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 278.1ºC

5-HT2A receptor agonist-1

5-HT2A receptor agonist-1 is a 5-HT2A receptor agonist with the EC50 of 5.54 nM. 5-HT2A receptor agonist-1 can be used for the research of mood disorders[1].

  • CAS Number: 2698331-34-7
  • MF: C15H22ClFN2
  • MW: 284.80
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ML138

ML138, a κ opioid receptor agonist, is a MLPCN probe[1].

  • CAS Number: 1355243-24-1
  • MF: C19H14Cl2N4OS
  • MW: 417.312
  • Catalog: Opioid Receptor
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 625.0±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 331.8±34.3 °C

trans-Tranilast

Trans-Tranilast is an antiallergic drug, used to treat bronchial asthma, allergic rhinitis and atopic dermatitis.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: 70806-55-2
  • MF: C18H17NO5
  • MW: 327.33100
  • Catalog: Angiotensin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

L 760735

L-760735 is a high affinity, selective and orally active NK1 receptor antagonist with an IC50 of 0.19 nM for human NK1 receptors. L-760735 exhibits anxiolytic and antidepressant-like effects[1].

  • CAS Number: 188923-01-5
  • MF: C26H29ClF7N5O2
  • MW: 611.98
  • Catalog: Neurokinin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bepotastine tosylate

Bepotastine tosylate is a selective and orally active second-generation histamine H1 receptor antagonist. Bepotastine tosylate has the potential for allergic rhinitis, allergic conjunctivitis and urticaria/pruritus research[1][2][3].

  • CAS Number: 1160415-45-1
  • MF: C28H33ClN2O6S
  • MW: 561.09
  • Catalog: Histamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GRA Ex-25

GRA Ex-25 is an inhibitor of glucagon receptor, with IC50 of 56 and 55 nM for rat and human glucagon receptors, respectively.

  • CAS Number: 307983-31-9
  • MF: C29H36F3N3O5
  • MW: 563.60800
  • Catalog: Glucagon Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Pheniramine maleate

Pheniramine Maleate ia an antihistamine and vasoconstrictor.

  • CAS Number: 132-20-7
  • MF: C20H24N2O4
  • MW: 356.416
  • Catalog: Histamine Receptor
  • Density: N/A
  • Boiling Point: 348.3ºC at 760 mmHg
  • Melting Point: 104-108°C
  • Flash Point: 164.5ºC

INT-777 R-enantiomer

INT-777 (R-enantiomer) is the R-enantiomer of INT-777, with EC50 of 4.79 μM for TGR5, and less potent than INT-777.

  • CAS Number: 1198786-98-9
  • MF: C27H46O5
  • MW: 450.651
  • Catalog: GPCR19
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 602.8±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 332.4±28.0 °C

CCG 203971

CCG-203971 is a second-generation RhoA/myocardin-related transcription factor A (MRTF-A) inhibitor. CCG-203971 potently targets RhoA/C-activated serum response element (SRE)-luciferase (IC50=6.2 μM).

  • CAS Number: 1443437-74-8
  • MF: C23H21ClN2O3
  • MW: 408.877
  • Catalog: Ras
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 656.0±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 350.5±31.5 °C

AZ 3451

AZ3451 is a protease-activated receptor-2 (PAR2) antagonist.

  • CAS Number: 2100284-59-9
  • MF: C30H27BrN4O3
  • MW: 571.46
  • Catalog: Protease-Activated Receptor (PAR)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

FLUNISOLIDE

Flunisolide hemihydrate is a corticosteroid, which is an orally active glucocorticoid receptor activator with anti-inflammatory activity. Flunisolide hemihydrate can induce eosinophil apoptosis, and is used for the research of asthma or rhinitis, and inflammation[1][2].

  • CAS Number: 77326-96-6
  • MF: C48H64F2O13
  • MW: 887.01100
  • Catalog: Apoptosis
  • Density: 1.33 g/cm3
  • Boiling Point: 581.8ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 305.7ºC