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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Met-Lys-Bradykinin

Methionyl-Lysyl-Bradykinin (Met-Lys-Bradykinin), a Bradykinin (HY-P0206) analogue, is a kinin[1][2].

  • CAS Number: 550-19-6
  • MF: C61H94N18O13S
  • MW: 1319.58000
  • Catalog: Bradykinin Receptor
  • Density: 1.46g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Prucalopride Succinate

Prucalopride succinate is a selective, high affinity 5-HT4 receptor agonist with pKi of 8.6/8.1 for 5-HT4a/4b.IC50 value:Target: 5-HT4 agonistin vitro: Prucalopride was a 5-HT(4) receptor agonist in the guinea-pig colon, as it induced contractions (pEC(50)=7.48+/-0.06; insensitive to a 5-HT(2A) or 5-HT(3) receptor antagonist, but inhibited by a 5-HT(4) receptor antagonist) as well as the facilitation of electrical stimulation-induced noncholinergic contractions (blocked by a 5-HT(4) receptor antagonist). Prucalopride did not cause relevant inhibition of 5-HT(2A), 5-HT(2B), or 5-HT(3), motilin or cholecystokinin (CCK(1)) receptor-mediated contractions, nor nicotinic or muscarinic acetylcholine receptor-mediated contractions, up to 10 microM [1].in vivo: Rat microdialysis studies revealed that prucalopride maximally increased ACh and histamine levels in the prefrontal cortex at 5 and 10 mg/kg, whereas PRX-03140 significantly increased cortical histamine levels at 50 mg/kg, failing to affect ACh release at doses lower than 150 mg/kg [2].

  • CAS Number: 179474-85-2
  • MF: C22H32ClN3O7
  • MW: 485.958
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

1-Isopropyl-1H-benzotriazole-5-carboxylic acid

GPR109 receptor agonist-1 (Compound 3a) is a highly selective agonist of the human orphan G-protein-coupled receptor GPR109b, with the pEC50 of 6.4. GPR109 receptor agonist-1 can be used for the research of cardio-metabolic diseases[1].

  • CAS Number: 306935-41-1
  • MF: C10H11N3O2
  • MW: 205.213
  • Catalog: GPR109A
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 413.9±18.0 °C at 760 mmHg
  • Melting Point: 229-230ºC
  • Flash Point: 204.1±21.2 °C

Reproterol

Reproterol is a dual acting β2-adrenoceptor agonist and PDE inhibitor. The theophylline constituent of Reproterol inhibits phosphodiesterase activity induced by adenylyl cyclase. Reproterol has the potential for asthma research[1][2].

  • CAS Number: 54063-54-6
  • MF: C18H23N5O5
  • MW: 389.41
  • Catalog: Adrenergic Receptor
  • Density: 1.47g/cm3
  • Boiling Point: 723.4ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 391.3ºC

benzetimide

Dexetimide ((+)-Benzetimide) is a high-affinity muscarinic receptor antagonist and a potent and persistent anticholinergic agent used to treat neuroleptic-induced parkinsonism[1].

  • CAS Number: 21888-98-2
  • MF: C23H26N2O2
  • MW: 398.92600
  • Catalog: mAChR
  • Density: 1.178g/cm3
  • Boiling Point: 543.9ºC at 760 mmHg
  • Melting Point: 181-183°
  • Flash Point: 282.7ºC

UCSF648

UCSF648 (Compound 5A6-48) is a chemical probe for the 5-HT5A serotonin receptor. UCSF648 weakly activates ADRA2A and MTNR1A[1].

  • CAS Number: 2637090-55-0
  • MF: C15H19ClN2O2S
  • MW: 326.84
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Azilsartan medoxomil

Azilsartan medoxomil(TAK 491) is an orally administered angiotensin II receptor type 1 antagonist with IC50 of 0.62 nM, which used in the treatment of adults with essential hypertension. IC50 Value: 0.62 nM [2]Target: AT1 receptorin vitro: In aortic endothelial cells, azilsartan inhibited cell proliferation at concentrations as low as 1 μmol/l, whereas valsartan showed little or no antiproliferative effects at concentrations below 10 μmol/l. Antiproliferative effects of azilsartan were also observed in cells lacking AT1 receptors[1].in vivo: Oral administration of 0.1-3 mg/kg olmesartan medoxomil reduced blood pressure; however, only the two highest doses significantly reduced blood pressure 24h after dosing. ED(25) values were 0.41 and 1.3 mg/kg for azilsartan medoxomil and olmesartan medoxomil, respectively [2]. Over a longer treatment period of 24 weeks, azilsartan medoxomil showed sustained BP-lowering efficacy, with the reduction in 24-hour mean SBP at week 24 significantly greater with azilsartan medoxomil 40 or 80 mg once daily than with valsartan 320 mg once daily. Mean reductions from baseline in mean clinic SBP and DBP as well as DBP by ABPM were also significantly greater with azilsartan medoxomil 40 or 80 mg once daily than with valsartan[3]. In 4 randomized controlled trials (3 published to date), azilsartan medoxomil/chlorthalidone 40 mg/12.5 mg and 40 mg/25 mg reduced blood pressure (BP) significantly more than comparators did, including an approximately 5-mm Hg greater BP reduction than olmesartan medoxomil/hydrochlorothiazide 40 mg/25 mg and azilsartan medoxomil/hydrochlorothiazide [4].Clinical trial: Effect of Azilsartan on Aldosterone in Post-menopausal Females . Phase not specified

  • CAS Number: 863031-21-4
  • MF: C30H24N4O8
  • MW: 568.534
  • Catalog: Angiotensin Receptor
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 748.0±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 406.2±35.7 °C

pan-KRAS-IN-3

pan-KRAS-IN-3 (Example 84) is a pan-KRAS inhibitor. pan-KRAS-IN-3 can be used for research of cancers[1].

  • CAS Number: 2875116-29-1
  • MF: C33H32F3N5O2
  • MW: 587.63
  • Catalog: Ras
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Hydroxyzine D4

Hydroxyzine D4 is deuterium labeled Hydroxyzine. Hydroxyzine is a heterocyclic histamine H1-receptor antagonist. Hydroxyzine has anticholinergic, anxiolytic and analgesic properties[1].

  • CAS Number: 2070014-84-3
  • MF: C21H23D4ClN2O2
  • MW: 378.93
  • Catalog: Histamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ondansetron

Ondansetron(GR38032) is a serotonin 5-HT3 receptor antagonist used mainly as anantiemetic (to treat nausea and vomiting), often following chemotherapy.IC50 Value: Target: 5- HT3 Receptorin vitro: 5-HT evoked transient inward currents (EC50 = 3.4 microM; Hill coefficient = 1.8) that were blocked by the 5-HT3 receptor antagonist ondansetron (IC50 = 103 pM) [1]. The 5-HT3A receptor antagonist ondansetron (0.3 nM) reversibly inhibited the 5-HT (30 microM) signal by 70% and at 3 nM it abolished the response [2].in vivo: Acute ondansetron administration at the lowest dose (0.1 mg/kg, IP) tested had no effect, while other doses (0.33 and 1 mg/kg, IP) produced improvements in auditory gating [3]. Different doses of ondansetron were injected intraperitoneally (i.p.) at fixed times during the day to determine both the sublethal (TD50) and lethal (LD50) doses, which were, respectively, 3.7 +/- 0.6 mg/kg and 4.6 +/- 0.5 mg/kg [4]. ondansetron (0.25-1.0 mg/kg, subcutaneously) given before the challenge dose of ethanol (2.4 g/kg, intraperitoneally) injection, significantly and dose dependently attenuated the expression of sensitization. In addition, ondansetron (1.0 mg/kg, subcutaneously) given before ethanol injection on days 1, 4, 7, and 10 significantly blocked the development (days 1, 4, 7, and 10), and expression (day 15) of sensitization to the locomotor stimulant effect of ethanol injection [5]. Toxicity: Ondansetron may be safe in lower doses used to prevent nausea and vomiting in radiation treatment or postoperatively. However, as there is a report that a lower dose of ondansetron prolonged the QT interval in healthy volunteers, this needs to be clarified by the FDA [6].

  • CAS Number: 99614-02-5
  • MF: C18H19N3O
  • MW: 293.363
  • Catalog: 5-HT Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 546.0±30.0 °C at 760 mmHg
  • Melting Point: 231 - 232ºC
  • Flash Point: 284.0±24.6 °C

PSB 1114

PSB-1114 tetrasodium is a potent, enzymatically stable, and subtype-selective P2Y2 receptor agonist with an EC50 of 134 nM. PSB-1114 tetrasodium displays >50-fold selectivity versus the P2Y4 (EC50 of 9.3 μM) and P2Y6 (EC50 of 7.0 μM) receptors[1].

  • CAS Number: 1657025-60-9
  • MF: C10H11F2N2Na4O13P3S
  • MW: 622.14
  • Catalog: P2Y Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AMN082 free base

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

  • CAS Number: 83027-13-8
  • MF: C28H28N2
  • MW: 465.45700
  • Catalog: mGluR
  • Density: N/A
  • Boiling Point: 533.7ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 321.5ºC

Substance P-Gly-Lys-Arg

Substance P-Gly-Lys-Arg, also known as β-Preprotachykinin (58-71), is an analog of Substance P (Substance P (HY-P0201))[1].

  • CAS Number: 123148-51-6
  • MF: C77H124N24O17S
  • MW: 1690.02
  • Catalog: Neurokinin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

β-CGRP (human)

β-CGRP, human is one of calcitonin peptides, acts via the complex of calcitonin-receptor-like receptor (CRLR) and receptor-activity-modifying protein (RAMP), with IC50s of 1 nM and 300 nM for CRLR/RAMP1 and CRLR/RAMP2 in cells.

  • CAS Number: 101462-82-2
  • MF: C162H267N51O48S3
  • MW: 3793.41
  • Catalog: Peptides
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Irbesartan-d6-1

Irbesartan-d6-1 is the deuterium labeled Irbesartan[1]. Irbesartan (SR-47436) is an orally active Ang II type 1 (AT1) receptor blocker (ARB). Irbesartan can relax the blood vessels, low blood pressure and increase the supply of blood and oxygen to the heart. Irbesartan can be used for the research of high blood pressure, heart failure, and diabetic kidney disease[2].

  • CAS Number: 2375621-21-7
  • MF: C25H22D6N6O
  • MW: 434.57
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MM 77 dihydrochloride

MM 77 dihydrochloride is a potent postsynaptic antagonist of the 5-HT1A receptor. MM 77 dihydrochloride exhibits anxiolytic-like activity[1][2].

  • CAS Number: 159187-70-9
  • MF: C19H29Cl2N3O3
  • MW: 418.358
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Budesonide

Budesonide is a glucocortical steroid with potent anti-inflammatory activity.

  • CAS Number: 51333-22-3
  • MF: C25H34O6
  • MW: 430.534
  • Catalog: Glucocorticoid Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 599.7±50.0 °C at 760 mmHg
  • Melting Point: 221-232ºC (dec.)
  • Flash Point: 201.8±23.6 °C

Herkinorin

Herkinorin is a potent and selective agonist of µ opioid receptor with a Ki of 45 nM Herkinorin is widely used for pain research[1].

  • CAS Number: 862073-77-6
  • MF: C28H30O8
  • MW: 494.53300
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ac-Asp(Glu-OH)-OH

β-Spaglumic acid (β-NAAG) is a competitive NAAG peptidase inhibitor (Ki=1 µM) that protects spinal cord neurons from excitotoxicity and hypoxic damage. β-Spaglumic acid is also a selective mGluR3 antagonist (mGluR3 receptor functions to regulate activity-dependent synaptic potentiation in the hippocampus). β-Spaglumic acid can be used in neuroprotection-related studies[1][2].

  • CAS Number: 4910-46-7
  • MF: C11H16N2O8
  • MW: 304.253
  • Catalog: mGluR
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 769.5±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 419.1±32.9 °C

Bopindolol

Bopindolol is an orally active antagonist of β-adrenoceptors (ARs) with partial agonist activity. Bopindolol is non-selective for β1- and β2-ARs and has low affinity for β3-AR subtype. Bopindolol is a prodrug of pindolol and can be used for essential and renovascular hypertension research[1][2].

  • CAS Number: 62658-63-3
  • MF: C23H28N2O3
  • MW: 380.48000
  • Catalog: Adrenergic Receptor
  • Density: 1.143 g/cm3
  • Boiling Point: 557ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 290.7ºC

A3AR antagonist 2

A3AR antagonist 2 (compound 18) is a potent Human A3 adenosine receptor antagonist with an Ki value of 4.54 nM[1].

  • CAS Number: 1144161-05-6
  • MF: C22H16N6O3
  • MW: 412.40100
  • Catalog: Adenosine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SOS1-IN-5

SOS1-IN-5 is a potent inhibitor of SOS1. SOS1-IN-5 is a pyrimidobicyclic derivative. SOS1-IN-5 blocks the activation of KRAS by interfering with RAS-SOS1 interaction, and achieves the purpose of broad-spectrum inhibition of KRAS activity. SOS1-IN-5 has the potential for the research of cancer diseases (extracted from patent WO2021203768A1, compound 4)[1].

  • CAS Number: 2716956-47-5
  • MF: C26H31F3N4O5
  • MW: 536.54
  • Catalog: Ras
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

L-152,804

L 152804 is an orally active and selective neuropeptide Y Y5 receptor (NPY5-R) antagonist, with a Ki of 26 nM for hY5. L 152804 causes weight loss in diet-induced obese mice by modulating food intake and energy expenditure[1][2].

  • CAS Number: 6508-43-6
  • MF: C23H26O4
  • MW: 366.45000
  • Catalog: Neuropeptide Y Receptor
  • Density: 1.23g/cm3
  • Boiling Point: 506.7ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 173ºC

Mesembrine-d3

Mesembrine-d3 ((+)-Mesembrine-d3) is the deuterium labeled Mesembrine. Mesembrine ((+)-Mesembrine) a main alkaloid that features an aryloctahydroindole skeleton. Mesembrine is a 5-HT transporter inhibitor with a Ki of 1.4 nM. Mesembrine also inhibits phosphodiesterase 4B (PDE4B) with an IC50 of 7.8 μM[1][2].

  • CAS Number: 1346600-05-2
  • MF: C17H20D3NO3
  • MW: 292.39
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Clenproperol-D7

Clenproperol-D7 is the deuterium labeled Clenproperol. Clenproperol is a β2-adrenergic agonist[1].

  • CAS Number: 1173021-09-4
  • MF: C11H9D7Cl2N2O
  • MW: 270.20700
  • Catalog: Adrenergic Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 109-111°C
  • Flash Point: N/A

HEAT hydrochloride

HEAT (BE2254) hydrochloride is a selective alpha 1 adrenergic receptor antagonist. HEAT hydrochloride, a phenethylamine derivative, shows pKis of 9, 9.1, and 8.57 for alpha 1a, alpha 1b and alpha 1c, respectively[1][2].

  • CAS Number: 30007-39-7
  • MF: C19H22ClNO2
  • MW: 331.83600
  • Catalog: Adrenergic Receptor
  • Density: N/A
  • Boiling Point: 492.8ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 251.9ºC

EMD 66684

EMD 66684 is an antagonist of Angiotensin II Type 1 (AT1) receptor. EMD 66684 shows potent binding affinities for the AT1 subtype Ang II receptor with an IC50 value of 0.7 nM. EMD 66684 also serves as an antiischemic cytoprotectant [1]-[5].

  • CAS Number: 1216884-39-7
  • MF: C28H31ClN8O2
  • MW: 547.051
  • Catalog: Angiotensin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Olodaterol

Olodaterol (BI1744) is a selective, long acting β2-adrenoceptor (β2-AR) agonist (EC50=0.1 nM and pKi= 9.14 for human β2-adrenoceptor, respectively). Olodaterol can be used for chronic obstructive pulmonary disease (COPD) and pulmonary fibrosis[1][2][3].

  • CAS Number: 868049-49-4
  • MF: C21H26N2O5
  • MW: 386.441
  • Catalog: Adrenergic Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 649.0±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 346.3±31.5 °C

BAY-6672 hydrochloride

BAY-6672 hydrochloride is a potent and selective human Prostaglandin F (FP) receptor antagonist with an IC50 value of 11 nM.

  • CAS Number: 2247520-31-4
  • MF: C26H28BrCl2N3O3
  • MW: 581.33
  • Catalog: Prostaglandin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

4-Methylhistamine hydrochloride

4-Methylhistamine (hydrochloride) is a potent, high affinity H4 receptor agonist Ki of 7 nM. 4-Methylhistamine (hydrochloride) displays more than 100-fold selectivity over other human histamine receptor subtypes[1].

  • CAS Number: 84103-51-5
  • MF: C6H12ClN3
  • MW: 161.63
  • Catalog: Histamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A