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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DPDPE TFA

DPDPE TFA, an opioid peptide, is a selective δ-opioid receptor (DOR) agonist with anticonvulsant effects[1].

  • CAS Number: 172888-59-4
  • MF: C30H39N5O7S2
  • MW: 645.79
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Adenosine 2',5'-diphosphate sodium

Adenosine 2',5'-diphosphate sodium is a competitive P2Y1 antagonist. Adenosine 2',5'-diphosphate sodium exhibits non-selective antagonism at recombinant and human platelet P2X1 receptors[1][2].

  • CAS Number: 154146-84-6
  • MF: C10H15N5O10P2.xNa
  • MW:
  • Catalog: P2Y Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tarafenacin

Tarafenacin(SVT-40776) is a highly selective M3 muscarinic receptor antagonist (Ki= 0.19 nM), ~200 fold selectivity over M2 receptor.IC50 value: 0.19 nM (Ki) [1]Target: M3 muscarinic receptorin vitro: SVT-40776 is highly selective for M(3) over M(2) receptors (Ki = 0.19 nmol.L(-1) for M(3) receptor affinity). SVT-40776 was the most potent in inhibiting carbachol-induced bladder contractions of the anti-cholinergic agents tested, without affecting atrial contractions over the same range of concentrations. SVT-40776 exhibited the highest urinary versus cardiac selectivity (199-fold) [1]. SVT-40776 has a much higher binding affinity (K(d) = 0.4 nM) to M5 mAChR than that of solifenacin (K(d) = 31 nM) with the same reeptor. The calculated binding free energy change (-2.3 ± 0.3 kcal/mol) from solifenacin to SVT-40776 is in good agreement with the experimentally derived binding free energy change (-2.58 kcal/mol), suggesting that our modeled M5 mAChR structure and its complexes with the antagonists are reliable [2].in vivo: In the guinea pig in vivo model, SVT-40776 inhibited 25% of spontaneous bladder contractions at a very low dose (6.97 microg.kg(-1) i.v), without affecting arterial blood pressure [1].

  • CAS Number: 385367-47-5
  • MF: C21H20F4N2O2
  • MW: 408.389
  • Catalog: mAChR
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 483.4±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 246.2±28.7 °C

Misoprostol acid

Misoprostol acid is an active metabolite of Misoprostol. Misoprostol is a synthetic analogue of prostaglandin E1 (PGE1), extensively absorbed, and undergoes rapid de-esterification to Misoprostol acid in the gastrointestinal tract after oral administration. Misoprostol can be used for non-steroidal anti-inflammatory drug-induced (NSAID) gastric ulcers[1]. Misoprostol is an oral agent used to induce labor[2].

  • CAS Number: 112137-89-0
  • MF: C21H36O5
  • MW: 368.508
  • Catalog: Prostaglandin Receptor
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 538.3±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 293.4±26.6 °C

ReN-1869 hydrochloride

ReN 1869 hydrochloride is a novel, selective histamine H1 receptor antagonist, which demonstrates affinity to the histamine H1 receptor (guinea pig brain) with Ki of 0.19±0.04 μM and the non-selective σ site (guinea pig brain) with Ki of 0.45 μM.

  • CAS Number: 170149-76-5
  • MF: C24H28ClNO2
  • MW: 397.938
  • Catalog: Histamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

A-437203

A-437203 is a selective D3 receptor antagonist with Ki of 71, 1.6, and 6220 nM for D2, D3, and D4 receptors, respectively.

  • CAS Number: 220519-06-2
  • MF: C20H27F3N6OS
  • MW: 456.52800
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ASP1126

ASP1126 is a selective and orally active sphingosine-1-phosphate (S1P) agonist, with EC50 values of 7.12 nM, 517 nM for hS1P1 and hS1P3, respectively. ASP1126 decreases the number of peripheral lymphocytes, naive T cells, central memory T cells and effector memory T cells in the peripheral blood. ASP1126 has the potential to be applied in clinical transplantation with improved safety profile[1].

  • CAS Number: 1228580-11-7
  • MF: C26H26ClF6NO5
  • MW: 581.93
  • Catalog: LPL Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CCR5 antagonist 3

CCR5 antagonist 3 (Compound 26) is a CCR5 antagonist with an IC50 of 15.90 nM. CCR5 antagonist 3 shows broad-spectrum anti-HIV-1 activities[1].

  • CAS Number: 1800570-92-6
  • MF: C30H41F2N5O2S
  • MW: 573.74
  • Catalog: HIV
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AMN082 dihydrochloride

AMN082, a selective, orally active, and brain penetrant mGluR7 agonist, directly activates receptor signaling via an allosteric site in the transmembrane domain. AMN082 potently inhibits cAMP accumulation and stimulates GTPγS binding (EC50 values, 64-290 nM) at transfected mammalian cells expressing mGluR7. AMN082 shows selectivity over other mGluR subtypes and selected ionotropic glutamate receptors. Antidepressant effects[1][2].

  • CAS Number: 97075-46-2
  • MF: C28H30Cl2N2
  • MW: 465.45700
  • Catalog: mGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Danirixin

Danirixin is a selective, and reversible CXCR2 antagonist, with IC50 of 12.5 nM for CXCL8.

  • CAS Number: 954126-98-8
  • MF: C19H21ClFN3O4S
  • MW: 441.904
  • Catalog: CXCR
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 533.1±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 276.2±30.1 °C

LY404039

LY404039 is an inhibitor for mGluR1(Ki=149 nM) and mGluR2(Ki= 92 nM), which can also inhibit dopamine receptor.IC50 Value:149 nM(Ki for mGlu2); 92 nM(Ki for mGlu3)[1]Target: mGluR1; mGluR2Metabotropic glutamate (mGlu) receptors have been shown to mediate a number of behaviors including emotionality and responsivity to stress as demonstrated by efficacy in preclinical and clinical studies.in vitro: Similar to LY354740, LY404039 is a nanomolar potent agonist at recombinant human mGlu2 and mGlu3 receptors (K(i) = 149 and 92, respectively) and in rat neurons expressing native mGlu2/3 receptors (Ki = 88). LY404039 is highly selective for mGlu2/3 receptors, showing more than 100-fold selectivity for these receptors, versus ionotropic glutamate receptors, glutamate transporters, and other receptors targeted by known anxiolytic and antipsychotic medications[1].in vivo: LY404039 attenuated amphetamine- and phencyclidine-induced hyperlocomotion (3-30 and 10 mg/kg, respectively). LY404039 (3-10 mg/kg) inhibited conditioned avoidance responding. LY404039 also reduced fear-potentiated startle in rats (3-30 microg/kg) and marble burying in mice (3-10 mg/kg), indicating anxiolytic-like effects. Importantly, LY404039 did not produce sedative effects or motor impairment as measured by rotarod performance and lack of escape failures in the conditioned avoidance task (at doses up to 30 and 10 mg/kg, respectively). LY404039 (10 mg/kg) also increased dopamine and serotonin release/turnover in the prefrontal cortex [3].Clinical trial: An Absolute Bioavailability Study of LY-2140023 and LY-404039 in Healthy Subjects Using the Intravenous Tracer Method. Phage1

  • CAS Number: 635318-11-5
  • MF: C7H9NO6S
  • MW: 235.214
  • Catalog: mGluR
  • Density: 1.9±0.1 g/cm3
  • Boiling Point: 600.3±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 316.8±31.5 °C

O-Butyryl timolol

Butyryltimolol, an effective prodrug of Timolol, improves the corneal penetration of Timolol[1]. Butyryltimolol is a β-adrenergic blocker[2].

  • CAS Number: 106351-79-5
  • MF: C17H30N4O4S
  • MW: 386.51000
  • Catalog: Adrenergic Receptor
  • Density: 1.169g/cm3
  • Boiling Point: 511.5ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 263.2ºC

Ondansetron-d3 hydrochloride

Ondansetron-d3 (GR 38032-d3) hydrochloride) is the deuterium labeled Ondansetron hydrochloride. Ondansetron hydrochloride (GR 38032 hydrochloride) is a serotonin 5-HT3 receptor antagonist used mainly as anantiemetic (to treat nausea and vomiting), often following chemotherapy[1][2].

  • CAS Number: 1346605-02-4
  • MF: C18H17D3ClN3O
  • MW: 296.39
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Pratosartan

Pratosartan is a selective angiotensin II receptor antagonist.

  • CAS Number: 153804-05-8
  • MF: C25H26N6O
  • MW: 426.51400
  • Catalog: Angiotensin Receptor
  • Density: 1.321g/cm3
  • Boiling Point: 692.92ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 372.864ºC

Ratic

Ranitidine is a potent, selective and orally active histamine H2-receptor antagonist with an IC50 of 3.3 μM that inhibits gastric secretion. Ranitidine is a weak inhibitor of CYP2C19 and CYP2C9[1][2].

  • CAS Number: 66357-35-5
  • MF: C13H22N4O3S
  • MW: 314.404
  • Catalog: Bacterial
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 437.1±45.0 °C at 760 mmHg
  • Melting Point: 69-70°C
  • Flash Point: 218.2±28.7 °C

PEN-221

PEN-221 is a Somatostatin receptor 2 (SSTR2)-targeting cytotoxic conjugate with an IC50 of 10 nM.

  • CAS Number: 1853254-97-3
  • MF: C83H109ClN14O20S4
  • MW: 1786.55
  • Catalog: Somatostatin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Phenoxybenzamine HCl

Phenoxybenzamine hydrochloride is a selective antagonist of both α-adrenoceptor and calmodulin that is commonly used for the treatment of hypertension, specifically caused by pheochromocytoma.

  • CAS Number: 63-92-3
  • MF: C18H23Cl2NO
  • MW: 340.287
  • Catalog: Adrenergic Receptor
  • Density: N/A
  • Boiling Point: 381.5ºC at 760 mmHg
  • Melting Point: 137.5°C
  • Flash Point: 184.5ºC

Cargutocin

Cargutocin, an oxytocin analogue, targets the oxytocin receptor and acts as a uterine contraction agent[1].

  • CAS Number: 33605-67-3
  • MF: C42H65N11O12
  • MW: 916.03200
  • Catalog: Oxytocin Receptor
  • Density: 1.208g/cm3
  • Boiling Point: 1490.2ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 855.1ºC

MLGFFQQPKPR-NH2

MLGFFQQPKPR-NH2 is a reversed Substance P peptide. Substance P is a neuropeptide[1].

  • CAS Number: 1802883-75-5
  • MF: C63H98N18O13S
  • MW: 1347.63
  • Catalog: Neurokinin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tamuzimod

Tamuzimod is a potent immunomodulator. Tamuzimod has S1P Receptor modulatory activity with EC50s <1 μM[1][2].

  • CAS Number: 2097854-81-2
  • MF: C21H13Cl3F3N5O3
  • MW: 546.71
  • Catalog: LPL Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

L-threo-(3,4-dihydroxyphenyl)serine hydrochloride

Droxidopa (L-DOPS) hydrochloride is a potent, orally active norepinephrine precursor. Droxidopa hydrochloride increases standing blood pressure, ameliorates symptoms of orthostatic hypotension and improves standing ability. Droxidopa hydrochloride has the potential for the research of neurogenic orthostatic hypotension (nOH) and alternative ADHD (attention deficit hyperactivity disorder)[1][2][3][4].

  • CAS Number: 1260173-94-1
  • MF: C9H12ClNO5
  • MW: 249.64800
  • Catalog: Adrenergic Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

LY-281217

LY-281217 is a potent mu-opioid agonist with analgesic effects[1].

  • CAS Number: 105027-75-6
  • MF: C32H42N4O6
  • MW: 578.69900
  • Catalog: Opioid Receptor
  • Density: 1.199g/cm3
  • Boiling Point: 786.4ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 429.4ºC

Cyamemazine

Cyamemazine is a neuroleptic agent that contains the phenothiazine chromophore. Cyamemazine is often used as an anxiolytic. Cyamemazine is a potent 5-HT3 (Ki of 12 nM), 5-HT2A (Ki = 1.5 nM) and 5-HT2C (Ki of 75 nM) receptors antagonist with antipsychotic activity[1][2].

  • CAS Number: 3546-03-0
  • MF: C19H21N3S
  • MW: 323.455
  • Catalog: 5-HT Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 479.0±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 243.5±28.7 °C

DREADD Agonist 21

DREADD agonist 21 is a potent human muscarinic acetylcholine M3 receptors (hM3Dq) agonist(EC50=1.7 nM).

  • CAS Number: 56296-18-5
  • MF: C17H18N4
  • MW: 278.352
  • Catalog: mAChR
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 470.1±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 238.1±31.5 °C

SCH 221510

SCH 221510 is a potent, orally active and selective NOP (nociceptin opioid receptor) agonist, with an EC50 of 12 nM and Ki of 0.3 nM. SCH 221510 shows an anxiolytic-like effect[1].

  • CAS Number: 322473-89-2
  • MF: C28H31NO
  • MW: 397.55
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

R 568 hydrochloride

Tecalcet Hydrochloride (R 568 Hydrochloride), an orally active calcimimetic compound, allosterically and positively modulates the calcium-sensing receptor (CaSR). Tecalcet Hydrochloride (R 568 Hydrochloride) increases the sensitivity to activation by extracellular Ca2+[1][2][3].

  • CAS Number: 177172-49-5
  • MF: C18H23Cl2NO
  • MW: 340.28700
  • Catalog: CaSR
  • Density: N/A
  • Boiling Point: 416.3ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 205.6ºC

Ramatroban

Ramatroban is a selective thromboxane A2 (TxA2, IC50=14 nM) antagonist, which also antagonizes CRTH2 (IC50=113 nM) by inhibiting PGD2 binding.

  • CAS Number: 116649-85-5
  • MF: C21H21FN2O4S
  • MW: 416.466
  • Catalog: Prostaglandin Receptor
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 654.7±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 349.7±34.3 °C

(4R,4aS,7aR,12bS)-3-(cyclopropylmethyl)-4a,7,9-trihydroxy-N-[2-(3-phenyl-1,2,4-oxadiazol-5-yl)propan-2-yl]-1,2,4,5,7a,13-hexahydro-4,12-methanobenzofuro[3,2-e]isoquinoline-6-carboxamide,4-methylbenzenesulfonic acid

Naldemedine (S-297995) tosylate is an orally active μ-opioid receptor antagonist (PAMORA)[1]. Naldemedine tosylate shows potent binding affinities (Ki=0.34, 0.43, 0.94 nM, respectively) and antagonist activities (IC50=25.57, 7.09, 16.1 nM, respectively) for recombinant human μ-, δ-, and κ- opioid receptors[2]. Naldemedine can be used in opioid-induced constipation (OIC) research[2]. Naldemedine tosylate is predicted to bind to 3CLpro encoded by SARS-CoV2 genome[3].

  • CAS Number: 1345728-04-2
  • MF: C39H42N4O9S
  • MW: 742.83700
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AR-C 118925XX

AR-C118925XX is a selective P2Y2 receptor antagonist. AR-C118925XX inhibits ATP-induced IL-6 production and phosphorylation of p38. AR-C118925XX also inhibits Bleomycin (HY-108345)-induced dermal fibrosis in mice. AR-C118925XX also inhibits ATP-induced tumor growth[1][2].

  • CAS Number: 216657-60-2
  • MF: C28H23N7O3S
  • MW: 537.592
  • Catalog: P2Y Receptor
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ML00253764

ML00253764 is a selective melanocortin receptor 4 (MC4R) antagonist, can induce apoptosis by inhibiting ERK1/2 and Akt phosphorylation, and has anticancer activity[1].

  • CAS Number: 681847-92-7
  • MF: C18H19BrClFN2O
  • MW: 413.712
  • Catalog: Cancer
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A