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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Ethybenztropine

Ethybenztropine (Ponalid) is a muscarinic receptor blocker. Ethybenztropine is an anticholinergic and antihistaminergic agent[1].

  • CAS Number: 524-83-4
  • MF: C22H27NO
  • MW: 321.45600
  • Catalog: mAChR
  • Density: 1.1g/cm3
  • Boiling Point: 422.8ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 124ºC

Dopamine serotonin antagonist-1

Dopamine serotonin antagonist-1 is a dual dopamine and serotonin receptor antagonist with Kis of 200, 2500, 420, 39, 84, 40 nM for dopamine D1, D2,D4, and serotonin S2A, S2C, S3, respectively.

  • CAS Number: 1977-07-7
  • MF: C18H20N4
  • MW: 292.37800
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Amitraz

Amitraz is a non-systemic acaricide and insecticide, with alpha-adrenergic agonist activity, interaction with octopamine receptors of the central nervous system and inhibition of monoamine oxidases and prostaglandin synthesis.

  • CAS Number: 33089-61-1
  • MF: C19H23N3
  • MW: 293.406
  • Catalog: Adrenergic Receptor
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 450.7±55.0 °C at 760 mmHg
  • Melting Point: 86-87°C
  • Flash Point: 226.4±31.5 °C

L-745870 trihydrochloride

L-745870 trihydrochloride is a potent, selective, brain-penetrant and orally active dopamine D4 receptor antagonist with a Ki of 0.43 nM. L-745870 trihydrochloride shows weaker affinity for D2 (Ki of 960 nM) and D3 (Ki of 2300 nM) receptors, and exhibits moderate affinity for 5-HT2 receptors, sigma sites and α-adrenoceptors[1][2][3].

  • CAS Number: 866021-03-6
  • MF: C18H20Cl2N4
  • MW: 363.28400
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ODQ

ODQ is a potent and selective soluble guanylyl cyclase (sGC, nitric oxide-activated enzyme) inhibitor. ODQ enhances the pro-apoptotic effects of Cisplatin in human mesothelioma cells[1].

  • CAS Number: 41443-28-1
  • MF: C9H5N3O2
  • MW: 187.155
  • Catalog: Apoptosis
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 321.3±25.0 °C at 760 mmHg
  • Melting Point: 160-170 °C
  • Flash Point: 148.1±23.2 °C

EP2 receptor antagonist-2

EP2 receptor antagonist-2 (CID891729) is an antagonist of EP2 receptor. EP2 receptor antagonist-2 inhibits the EP2 receptor activation induced by PGE2. EP2 receptor antagonist-2 also suppresses lactate dehydrogenase (LDH) release induced by N-methyl-D-aspartate (NMDA)[1].

  • CAS Number: 615273-95-5
  • MF: C15H14F3N3O
  • MW: 309.29
  • Catalog: Prostaglandin Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 451.8±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 227.0±31.5 °C

JZP 361

JZP-361 is a potent and reversible inhibitor of human recombinant MAGL (hMAGL, IC50=46 nM), and has almost 150-fold higher selectivity over human recombinant fatty acid amide hydrolase (hFAAH, IC50=7.24 μM) and 35-fold higher selectivity over human α/β-hydrolase-6 (hABHD6, IC50=1.79 μM). JZP-361 represents a dual-acting pharmacological tool possessing both MAGL inhibitory and antihistaminergic activities[1].

  • CAS Number: 1680193-80-9
  • MF: C22H20ClN5O
  • MW: 405.880
  • Catalog: Histamine Receptor
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 611.7±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 323.8±34.3 °C

Preladenant-d3

Preladenant-d3 (SCH-420814-d3) is the deuterium labeled Preladenant. Preladenant is a potent and competitive antagonist of the human adenosine A2A receptor with a Ki of 1.1 nM and has over 1000-fold selectivity over other adenosine receptors[1][2].

  • CAS Number: 1346599-84-5
  • MF: C25H26D3N9O3
  • MW: 506.57
  • Catalog: Adenosine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

KRAS G12C inhibitor 25

KRAS G12C inhibitor 25 is a KRAS G12C inhibitor. KRAS G12C inhibitor 25 inhibits SOSl-assisted GDP/GTP exchanging activity of KRAS-G12C mutant (IC50=0.48 nM). From WO2021216770A1 compound 3[1].

  • CAS Number: 2734060-73-0
  • MF: C32H41N7O2
  • MW: 555.71
  • Catalog: Ras
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Montelukast sodium

Montelukast sodium is a potent, selective CysLT1 receptor antagonist.

  • CAS Number: 151767-02-1
  • MF: C35H35ClNNaO3S
  • MW: 608.165
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: 750.5ºC at 760mmHg
  • Melting Point: 115 °C(dec.)
  • Flash Point: 407.7ºC

KW-8232

KW-8232, an orally active anti-osteoporotic agent, and can reduces the biosynthesis of PGE2[1].

  • CAS Number: 217813-15-5
  • MF: C37H39ClN4O5S
  • MW: 687.24700
  • Catalog: SARS-CoV
  • Density: N/A
  • Boiling Point: 805.5ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 440.9ºC

Ulocuplumab

Ulocuplumab (Anti-Human CXCR4 Recombinant Antibody/BMS-936564/MDX1338) is a fully human IgG4 anti-CXCR4 antibody. Ulocuplumab induces apoptosis and inhibits CXCL12 mediated CXCR4 activation-migration of chronic lymphocytic leukemia (CLL). Ulocuplumab exhibits antitumor activity in established tumors including acute myeloid leukemia (AML), non-Hodgkin lymphoma (NHL), and multiple myeloma xenograft models[1][2].

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

L-733,060 hydrochloride

L-733060 hydrochloride is a potent tachykinin NK1 receptor antagonist. L-733060 hydrochloride inhibits neurogenic plasma extravasation at doses that do not cause adverse cardiovascular effects in rodents and also acts as an antitumoral agent[1][2].

  • CAS Number: 148687-76-7
  • MF: C20H20ClF6NO
  • MW: 439.82200
  • Catalog: Neurokinin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Olanzapine

Olanzapine(LY170053) is a high affinity for 5-HT2 serotonin and D2 dopamine receptor antagonist.IC50 Value:Target: 5-HT ReceptorOlanzapine is a thienobenzodiazepine that blocks especially the serontonin (5-hydroxytryptamine [5-HT]) 5-HT2A and the dopamine D2 receptors (Ki values are 4 and 11 nM respectively) as well as muscarinic (M1), histamine (H1), 5-HT2C, 5-HT3 to 5-HT6, adrenergic (α(l)), and D4 receptors. Atypical antipsychotic for the treatment of schizophrenia. Olanzapine displays anticholinergic properties.

  • CAS Number: 132539-06-1
  • MF: C17H20N4S
  • MW: 312.432
  • Catalog: Apoptosis
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 476.0±55.0 °C at 760 mmHg
  • Melting Point: 195°C
  • Flash Point: 241.7±31.5 °C

Ro 22-9194

Ro 22-9194 inhibits aggregation and thromboxane Az (TXA2) synthetase activity in rabbit and human platelets. Ro 22-9194 has a potent inhibitory action against various types of model arrhythmias. Ro 22-9194 has non-cholinergic cardiac depressant properties with its vasodilating action[1][2].

  • CAS Number: 106134-33-2
  • MF: C19H27Cl2N3O
  • MW: 384.34300
  • Catalog: Prostaglandin Receptor
  • Density: N/A
  • Boiling Point: 494.1ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 252.6ºC

Pronethalol-d6

Pronethalol-d6 ((±)-Pronethalo-d6) is the deuterium labeled Pronethalol. Pronethalol ((±)-Pronethalo) is a non-selective β-adrenergic antagonist. Pronethalol is a potent inhibitor of Sox2 expression. Pronethalol protects against and to reverse Digitalis-induced ventricular arrhythmias and limits the cerebral arteriovenous malformation (AVMs)[1][2][3].

  • CAS Number: 1329805-79-9
  • MF: C15H13D6NO
  • MW: 235.35
  • Catalog: Adrenergic Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

FR167344 free base

FR167344 free base is an orally active, nonpeptide bradykinin receptor B2 antagonist. FR167344 free base shows a high affinity binding to the B2 receptor with an IC50 value of 65 nM and no binding affinity for the B1 receptor.

  • CAS Number: 215258-13-2
  • MF: C30H28BrCl2N5O4
  • MW: 673.38
  • Catalog: Bradykinin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BTRX-335140(CYM-53093

BTRX-335140 (CYM-53093) is a potent and selective, orally active κ opioid receptor (KOR) antagonist, has antagonist activity for κOR, μOR and δOR with IC50 values of 0.8 nM, 110 nM, and 6500 nM, respectively.BTRX-335140 endows with favorable in vitro ADMET and in vivo pharmacokinetic profiles and medication-like duration of action in rats. BTRX-335140 can distribute well into the CNS. ADMET (absorption, distribution, metabolism, excretion, and toxicity) [1].

  • CAS Number: 2244614-14-8
  • MF: C25H32FN5O2
  • MW: 453.55
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CM 572

A potent, selective, irreversible sigma-2 receptor partial agonist with Ki of 14.6 nM, >700-fold selectivity over sigma-1 receptors; induces dose-dependent cell death in SK-N-SH cells with EC50 of 7.6 uM, also demonstrates selective cytotoxic activity against PANC-1 pancreatic and MCF-7 breast cancer cell lines, with no significant effect on normal cells.

  • CAS Number: 1121932-91-9
  • MF: C22H23FN4O2S
  • MW: 426.51
  • Catalog: Sigma Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

L-Glutamine

L-Glutamine is a non-essential amino acid present abundantly throughout the body and is involved in gastrointestinal disorders.Target: mGluRGlutamine (abbreviated as Gln or Q) is one of the 20 amino acids encoded by the standard genetic code. It is not recognized as an essential amino acid, but may become conditionally essential in certain situations, including intensive athletic training or certain gastrointestinal disorders. Its side-chain is an amide formed by replacing the side-chain hydroxyl of glutamic acid with an amine functional group, making it the amide of glutamic acid. Its codons are CAA and CAG. In human blood, glutamine is the most abundant free amino acid, with a concentration of about 500-900 μmol/L. Glutamine is synthesized by the enzyme glutamine synthetase from glutamate and ammonia. The most relevant glutamine-producing tissue is the muscle mass, accounting for about 90% of all glutamine synthesized. Glutamine is also released, in small amounts, by the lung and the brain. Although the liver is capable of relevant glutamine synthesis, its role in glutamine metabolism is more regulatory than producing, since the liver takes up large amounts of glutamine derived from the gut. The most eager consumers of glutamine are the cells of intestines, the kidney cells for the acid-base balance, activated immune cells, and manycancer cells. In respect to the last point mentioned, different glutamine analogues, such as DON, Azaserine or Acivicin, are tested as anticancer drugs.

  • CAS Number: 56-85-9
  • MF: C5H10N2O3
  • MW: 146.145
  • Catalog: mGluR
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 353.5±52.0 °C at 760 mmHg
  • Melting Point: 185ºC
  • Flash Point: 167.6±30.7 °C

PSB-SB-487

Potent, allosteric GPR55 antagonist

  • CAS Number: 1399049-81-0
  • MF: C26H32O4
  • MW: 408.53
  • Catalog: GPR55
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Dermorphin TFA

Dermorphin TFA is a natural heptapeptide μ-opioid receptor (MOR) agonist found in amphibian skin. Inhibition of neuropathic pain[1].

  • CAS Number: 78331-26-7
  • MF: C42H51F3N8O12
  • MW: 916.89600
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PRX-08066 Maleic acid

PRX-08066 is a selective 5-hydroxytryptamine receptor 2B (5-HT2BR, IC50= 3.4 nM) antagonist that causes selective vasodilation of pulmonary arteries.

  • CAS Number: 866206-55-5
  • MF: C23H21ClFN5O4S
  • MW: 517.96
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

α-Helical CRF (12-41) trifluoroacetate salt

a-Helical Corticotropin Releasing Factor (12-41) is a 30 amino acids long, α-helical analogue of corticotropin releasing factor/hormone. Corticotropin releasing factor (CRF) is a hypothalamic hormone, which stimulates the secretion of adrenocorticotrophic hormone (ACTH). a-Helical Corticotropin Releasing Factor (12-41) would suppress the stimulatory effect[1][2].

  • CAS Number: 158535-55-8
  • MF: C152H251N43O47S2
  • MW: 3497.009
  • Catalog: CRFR
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(S)-timolol maleate

(S)-Timolol maleate, is a potent non-selective β-adrenergic receptor antagonist (Ki values are 1.97 and 2.0 nM for β1 and β2 receptor subtypes respectively). IC50 Value: 1.97 nM(Ki for β1); 2.0 nM(Ki for β2)Target: β-adrenergic receptor(S)-Timolol, 50% bioavailability following oral administration. Does not cross the blood brain barrier. Timolol maleate does appear to have some local anesthetic properties in human cornea after chronic use by susceptible individuals.

  • CAS Number: 26921-17-5
  • MF: C17H28N4O7S
  • MW: 432.492
  • Catalog: Adrenergic Receptor
  • Density: N/A
  • Boiling Point: 704.6ºC at 760 mmHg
  • Melting Point: 202-203 °C(lit.)
  • Flash Point: 380ºC

MK-571

MK-571 sodium salt is a selective, orally active leukotriene D4 receptor antagonist, with Kis of 0.22 and 2.1 nM in guinea pig and human lung membranes.

  • CAS Number: 115103-85-0
  • MF: C26H26ClN2NaO3S2
  • MW: 537.069
  • Catalog: Leukotriene Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PD 102807

PD 102807 is a M4 muscarinic receptor antagonist with an IC50 of 90.7 nM. PD 102807 inhibits M1, M2, M3, M5 muscarinic receptor with IC50s of 6558.7, 3440.7, 950.0, and 7411.7 nM, respectively[1]. Antidyskinetic effect.

  • CAS Number: 23062-91-1
  • MF: C23H24N2O4
  • MW: 392.45
  • Catalog: mAChR
  • Density: 1.34g/cm3
  • Boiling Point: 586ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 308.2ºC

BAN ORL 24

BAN ORL 24 free base is a nociceptin/orphanin FQ (N/OFQ) peptide receptor (NOP) antagonist. BAN ORL 24 free base has antagonistic effect for nociceptin (NOP) receptor with KI value of 0.24 nM in CHO cell. BAN ORL 24 free base can be used for the research of cancer and analgesic[1].

  • CAS Number: 475150-69-7
  • MF: C27H35N3O2
  • MW: 433.59
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AT-121

AT-121 is a bifunctional nociception and mu opioid receptor agonist, with Kis of 3.67 and 16.49 nM, respectively. AT-121 is a safe, non-addictive analgesic, and shows antinociceptive and antiallodynic effects[1].

  • CAS Number: 2099681-31-7
  • MF: C24H38N4O3S
  • MW: 462.65
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

[Leu31,Pro34]-Neuropeptide Y(human,rat)

[Leu31,Pro34]-Neuropeptide Y(human,rat) is a specific neuropeptide Y Y1 receptor agonist. [Leu31,Pro34]-Neuropeptide Y(human,rat) slao inhibits Y4, Y5. [Leu31,Pro34]-Neuropeptide Y(human,rat) can increase blood pressure in anesthetized rats and increases food intake[1][2].

  • CAS Number: 132699-73-1
  • MF: C189H283N54O56S
  • MW: 4240.67046
  • Catalog: Neuropeptide Y Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A