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.


Anti-infection >
Arenavirus Bacterial CMV Enterovirus Filovirus Fungal HBV HCV HIV HSV Influenza Virus Parasite Reverse Transcriptase RSV SARS-CoV
Antibody-drug Conjugate >
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15-PGDH 5 alpha Reductase 5-Lipoxygenase Acetyl-CoA Carboxylase Acyltransferase Adenosine Deaminase Adenosine Kinase Aldehyde Dehydrogenase (ALDH) Aldose Reductase Aminopeptidase Angiotensin-converting Enzyme (ACE) ATGL ATP Citrate Lyase Carbonic Anhydrase Carboxypeptidase Cathepsin CETP COMT Cytochrome P450 Dipeptidyl Peptidase Dopamine β-hydroxylase E1/E2/E3 Enzyme Elastase Enolase FAAH FABP Factor Xa Farnesyl Transferase Fatty Acid Synthase (FAS) FXR Glucokinase GSNOR Gutathione S-transferase HCV Protease Hexokinase HIF/HIF Prolyl-Hydroxylase HIV Integrase HIV Protease HMG-CoA Reductase (HMGCR) HSP Indoleamine 2,3-Dioxygenase (IDO) Isocitrate Dehydrogenase (IDH) Lactate Dehydrogenase LXR MAGL Mineralocorticoid Receptor Mitochondrial Metabolism MMP Nampt NEDD8-activating Enzyme Neprilysin PAI-1 PDHK PGC-1α Phosphatase Phosphodiesterase (PDE) Phospholipase Procollagen C Proteinase Proteasome Pyruvate Kinase RAR/RXR Renin ROR Ser/Thr Protease SGK Stearoyl-CoA Desaturase (SCD) Thrombin Tryptophan Hydroxylase Tyrosinase Xanthine Oxidase
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Tegaserod maleate

Tegaserod maleate is a partial agonist of the 5-HT4 receptor; stimulates the peristaltic reflex and accelerates gastrointestinal transit.IC50 value:Target: 5-HT4 agonistIn an in vivo model for peripheral nerve regeneration, mice receiving tegaserod at the site of injury showed enhanced recovery compared to control mice receiving vehicle control as evidenced by functional measurements and histology [1]. Treatment with fluoxetine (10 mg · kg(-1) · day(-1), days 36-42), tegaserod (1 mg · kg(-1) · day(-1), day 43), or the combination of both, reduced visceral hypersensitivity and plasma 5-HT levels [2]. Intravenous or intraduodenal tegaserod (0.3-1.0 mg.kg(-1)) had no inhibitory effect on mesenteric and colonic blood flow. Peroral treatment of rats with alosetron or tegaserod for 7 days did not modify mesenteric haemodynamics at baseline and after blockade of nitric oxide synthesis [3].

  • CAS Number: 189188-57-6
  • MF: C20H27N5O5
  • MW: 417.459
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: 661.4ºC at 760 mmHg
  • Melting Point: 180-183ºC
  • Flash Point: 353.8ºC

(D-Pro2,D-Trp6.8,Nle10)-Neurokinin B

(D-Pro2,D-Trp6,8,Nle10)-Neurokinin B is a competitive antagonist of Neurokinin B (Neurokinin Receptor) with a pA2 of 5.5. (D-Pro2,D-Trp6,8,Nle10)-Neurokinin B shows no influence on Substance P or Neurokinin A[1].

  • CAS Number: 109212-72-8
  • MF: C67H87N15O14
  • MW: 1326.50000
  • Catalog: Neurokinin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MCH (salmon)

Melanin Concentrating Hormone, salmon is a 19-amino-acid neuropeptide initially identified in the pituitary gland of teleost fish, which regulates food intake, energy balance, sleep state, and the cardiovascular system. Melanin-concentrating hormone is a ligand for an orphan G protein-coupled receptor (SLC-1/GPR24) and MCHR2.

  • CAS Number: 87218-84-6
  • MF: C89H139N27O24S4
  • MW: 2099.48000
  • Catalog: Peptides
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PF-04781340

A potent, selective, CNS penetrant 5-HT2C receptor agonist with Ki of 3 nM and EC50 of 9 nM, without significant P-gp efflux liability; displays >150-fold selectivity over 5-HT2B receptors agonism (EC50=1484 nM); exhibits good metabolic stability in human liver microsomes (HLM) and moderate to good passive permeability in RRCK cells.

  • CAS Number: 1648726-56-0
  • MF: C17H21N3
  • MW: 267.376
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Sultopride

Sultopride is a selective antagonist of dopamine D2 receptor.

  • CAS Number: 53583-79-2
  • MF: C17H26N2O4S
  • MW: 354.46400
  • Catalog: Dopamine Receptor
  • Density: 1.16g/cm3
  • Boiling Point: 530ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 274.3ºC

TRV130 (Racemate)

Oliceridine Racemate (TRV130 Racemate) is the racemate of Oliceridine. Oliceridine is a novel mu opioid receptor (MOR) agonist that preferentially activates G-protein versus β-arrestin signaling pathways coupled to MORs.

  • CAS Number: 1401028-25-8
  • MF: C22H30N2O2S
  • MW: 386.55100
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AM281

AM281 is a selective CB1 receptor antagonist with an IC50 of 9.91 nM. AM281 inhibits CB2 receptor with an IC50 of 13000 nM[1].

  • CAS Number: 202463-68-1
  • MF: C21H19Cl2IN4O2
  • MW: 557.212
  • Catalog: Cannabinoid Receptor
  • Density: 1.7±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

α-Conotoxin MI trifluoroacetate salt

α-Conotoxin M I is a potent and selective inhibitor of mAChR and α1β1γδ nAChR, but has no effect on nicotine-stimulated dopamine release. α-Conotoxins are small, disulfide-rich peptides that competitively inhibit muscle and neuronal nicotinic AChRs[1][2].

  • CAS Number: 88217-10-1
  • MF: C58H88N22O17S4
  • MW: 1493.72000
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ubrogepant

Ubrogepant (MK-1602) is a novel oral calcitonin gene-related peptide receptor (CGRP) antagonist in development for acute treatment of migraine[1].

  • CAS Number: 1374248-77-7
  • MF: C29H26F3N5O3
  • MW: 549.54400
  • Catalog: CGRP Receptor
  • Density: 1.45±0.1 g/cm3(Predicted)
  • Boiling Point: 729.4±60.0 °C(Predicted)
  • Melting Point: N/A
  • Flash Point: N/A

VCE-004.8

VCE-004.8, a semi-synthetic multitarget cannabinoquinoid, is a specific PPARγ and CB2 receptor dual agonist with potent anti-inflammatory activity[1]. VCE-004.8 inhibits prolyl-hydroxylases (PHDs) and activates the HIF pathway. VCE-004.8 attenuates adipogenesis and prevents diet-induced obesity[2].

  • CAS Number: 1818428-24-8
  • MF: C28H35NO3
  • MW: 433.58
  • Catalog: PPAR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ELN-441958

ELN-441958 is a potent, neutral antagonist of B1 receptor, inhibits the binding of the B1 agonist ligand [3H]DAKD to IMR-90 cells with Ki of 0.26 nM. ELN-441958 is highly selective for B1 over B2 receptors, and >500/ 2000-fold selective for the B1 over μ/δ-opioid receptor.IC50 value: 0.26 nM (Ki)Target: B1 Receptorin vitro: ELN-441958 is a novel small molecule bradykinin B1 receptor antagonist, based on the inhibition of agonist-induced increases in intracellular calcium in native and recombinant cells. ELN-441958 does not inhibit the activation of the human bradykinin B2 receptor at concentrations up to 10 μM, showing that it is highly selective for B1 over B2 receptors. ELN-441958 also displays good selectivity for B1 over other receptors examined in a broad screening panel. It is >500-fold and >2000-fold selective for the B1 receptor over the human μ- and δ-opioid receptor, the most potent off-target activity identified. In IMR-90 cells expressing the native human B1 receptor, ELN-441958 produced a concentration-dependent antagonism of the DAKD-induced calcium mobilization with a KB of 0.12 nM. [1]in vivo: ELN-441958 is essentially completely absorbed and produces high plasma levels after oral administration in rhesus monkeys.ELN-441958 has a moderate clearance and volume of distribution in both species following i.v. administration, consistent with the high metabolic stability in rat, rhesus, and human microsomes. ELN-441958 has high oral exposure and moderate plasma half-lives in rats and rhesus monkeys. The oral availability of ELN441958 in rats was 57%. ELN-441958 dose-dependently reduced carrageenan-induced thermal hyperalgesia in a rhesus monkey tail-withdrawal model, with an ED50 3 mg/kg s.c. [1]

  • CAS Number: 913064-47-8
  • MF: C29H29ClN4O2
  • MW: 501.01900
  • Catalog: Bradykinin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

OT antagonist 1

OT antagonist 1 (Compound 4) is a potent, selective Oxytocin antagonist with a Ki of 50 nM.

  • CAS Number: 479080-38-1
  • MF: C22H22N4O3
  • MW: 390.44
  • Catalog: Oxytocin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CXCR4 probe 1

CXCR4 probe 1 (compound 5) is a potent and specific CXCR4-targeted PET tracer with an IC50 value of 6.9 nM against CXCR4-specific antagonist peptide, TN14003. CXCR4 probe 1 has potential to be used as CXCR4-specific imaging probe to diagnose and monitor the prognosis of inflammatory diseases, CXCR4-positive tumors, and metastatic cancers[1].

  • CAS Number: 2077985-50-1
  • MF: C24H3018FN5O4S
  • MW: 502.59
  • Catalog: CXCR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(R)-(+)-Carvedilol

(R)-Carvedilol ((R)-BM 14190), the R-enantiomer of Carvedilol, is a non-selective β/α-1 blocker. (R)-Carvedilol exerts protection against the vascular or cardiac toxicity of Doxorubicin (DOX)[1].

  • CAS Number: 95093-99-5
  • MF: C24H26N2O4
  • MW: 406.47400
  • Catalog: Adrenergic Receptor
  • Density: 1.25g/cm3
  • Boiling Point: 655.2ºC at 760 mmHg
  • Melting Point: 114-115ºC
  • Flash Point: 350.1ºC

SB 265610

SB-265610 is a selective, competitive, nonpeptide and allosteric CXCR2 antagonist. SB-265610 blocks rat cytokine-induced neutrophil chemoattractant-1 (CINC-1)-induced calcium mobilization and neutrophil chemotaxis with IC50s of 3.7 nM and 70 nM, respectively[1][2].

  • CAS Number: 211096-49-0
  • MF: C14H9BrN6O
  • MW: 357.16500
  • Catalog: CXCR
  • Density: 1.779 g/cm3
  • Boiling Point: 527ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 272.5ºC

Glucocorticoid receptor-IN-1

Glucocorticoid receptor-IN-1 (Compound WX002) is a selective glucocorticoid receptor (GR) modulator with anti-inflammatory effect. Glucocorticoid receptor-IN-1 exhibits very good transcriptional repressive activity with an IC50 of 2.11 nM against hMMP1, and transcriptional activation activity with an EC50 of 5.59 nM against MMTV[1].

  • CAS Number: 2662908-25-8
  • MF: C24H19F4N7O2
  • MW: 513.45
  • Catalog: Glucocorticoid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TIP-39 trifluoroacetate salt

TIP 39, Tuberoinfundibular Neuropeptide is a neuropeptide and parathyroid hormone 2 receptor (PTH2R) agonist. TIP 39 is highly conserved among species. TIP39 from all species activates adenylyl cyclase and elevates intracellular calcium levels through parathyroid hormone 2 receptor (PTH2R)[1].

  • CAS Number: 277302-47-3
  • MF: C202H325N61O54S
  • MW:
  • Catalog: Adenylate Cyclase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GR 159897

GR 159897 is a highly potent, selective, competitive, brain-penetrated non-peptide antagonist at tachykinin NK2 receptors, inhibits binding of [3H]GR100679 to hNK2-CHO cells and rat colon membranes with pKis of 9.51 and 10, respectively. Antagonizes bronchoconstriction, with anxiolytic-like activity[1].

  • CAS Number: 158848-32-9
  • MF: C23H27FN2O2S
  • MW: 414.54
  • Catalog: Neurokinin Receptor
  • Density: 1.29g/cm3
  • Boiling Point: 600.2ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 316.8ºC

Povafonidine

Povafonidine (PGE-6201204) is a potent alpha-2 adrenoreceptor agonist. Povafonidine can constrict blood vessels and reduce mucosal congestion. Povafonidine can be used for nasal congestion research[1].

  • CAS Number: 177843-85-5
  • MF: C11H13N5
  • MW: 215.25
  • Catalog: Adrenergic Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ro 6842262

LPA1 antagonist 1 is a highly selective Lysophosphatidic Acid receptor-1 (LPA1) antagonist with an IC50 of 25 nM.

  • CAS Number: 1396006-71-5
  • MF: C28H26N4O4
  • MW: 482.53000
  • Catalog: LPL Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

N6-Cyclohexyladenosine

N6-Cyclohexyladenosine is a selective A1 receptor agonist (EC50 = 8.2 nM). IC50 value: 8.2 nM (EC50)Target: A1 receptorin vivo: N6-Cyclohexyladenosine exerts anticonvulsant effects and protects against neuronal death. CHA was also found to inhibit the pressor effects of lumbar sympathetic nerve stimulation in rats.

  • CAS Number: 36396-99-3
  • MF: C16H23N5O4
  • MW: 349.38500
  • Catalog: Adenosine Receptor
  • Density: 1.71g/cm3
  • Boiling Point: 675.2ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 362.1ºC

Syk inhibitor II

Syk Inhibitor II is a potent, high selective and ATP-competitive Syk inhibitor with an IC50 of 41 nM. Syk Inhibitor II inhibits 5-HT release from RBL-cells with an IC50 of 460 nM. Syk Inhibitor II shows less potent against other kinases and has anti-allergic effect[1].

  • CAS Number: 726695-51-8
  • MF: C14H15F3N6O
  • MW: 340.304
  • Catalog: 5-HT Receptor
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 541.6±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 281.4±32.9 °C

Viminol

Viminol is a centrally acting analgesic agent. Viminol also shows antitussive activity[1][2].

  • CAS Number: 21363-18-8
  • MF: C21H31ClN2O
  • MW: 362.94
  • Catalog: Opioid Receptor
  • Density: 1.07g/cm3
  • Boiling Point: 321.3ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 148.1ºC

Vorbipiprant

Vorbipiprant (CR6086) is an EP4 receptor antagonist, serving as a targeted immunomodulator. Thus, Vorbipiprant is also a potential immune checkpoint inhibitor, to turn cold tumors into hot tumors. Vorbipiprant also antagonizes PGE2-stimulated cAMP production (IC50=22 nM). Vorbipiprant exhibit striking DMARD effects in rodents, and anti-inflammatory activity to inhibt immune-mediated inflammatory diseases[1][2].

  • CAS Number: 1417742-86-9
  • MF: C26H27F3N2O3
  • MW: 472.50
  • Catalog: Prostaglandin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

trans-Isoferulic acid-d3

trans-Isoferulic acid-d3 is the deuterium labeled trans-Isoferulic acid[1]. trans-Isoferulic acid (trans-3-Hydroxy-4-methoxycinnamic acid) is an aromatic acid isolated from the roots of Clematis florida var. plena. trans-Isoferulic acid exhibits anti-inflammatory activity[2].trans-isoferulic acid suppresses NO and PGE2 production through the induction of Nrf2-dependent heme oxygenase-1 (HO-1)[3].

  • CAS Number: 1028203-97-5
  • MF: C10H7D3O4
  • MW: 197.20200
  • Catalog: Prostaglandin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Octreotide pamoate

Octreotide (SMS 201-995) pamoate is a somatostatin receptor agonist and synthetic octapeptide endogenous somatostatin analogue. Octreotide pamoate can bind to the somatostatin receptors which are mainly subtypes 2, 3 and 5. Octreotide pamoate increases Gi activity and reduces intracellular cAMP production. Octreotide pamoate has antitumor activity, mediates apoptosis and may also be used in disease studies in acromegaly[1][2].

  • CAS Number: 135467-16-2
  • MF: C49H66N10O10S2.xC23H16O6
  • MW:
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GPR120 modulator 2

GPR120 modulator 2 is useful for modulating G protein-coupled receptor 120 (GPR120).

  • CAS Number: 1050506-87-0
  • MF: C20H18ClNO3S
  • MW: 387.88000
  • Catalog: GPR120
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Domperidone

Domperidone is a dopamine blocker and an antidopaminergic reagent.Target: Dopamine ReceptorDomperidone is a useful alternative to metoclopramide for treatment of gastroparesis due to better tolerability. Effectiveness and side-effects from domperidone may be influenced by patient-related factors including polymorphisms in genes encoding drug-metabolizing enzymes, drug transporters, and domperidone targets [1]. Domperidone is a dopamine D(2) receptor antagonist, which has been used as antiemetic agent in human beings. The percentage recovery of domperidone from wastewater was 95.0%. Celiprolol was used as the internal standard to access the percentage extraction of domperidone from wastewater [2]. Domperidone, a dopamine antagonist that does not easily cross the blood-brain barrier, is considered the gold standard for treating gastrointestinal symptoms in patients with Parkinson's disease (PD) because the risk of developing extrapyramidal adverse effects is considered minimal [3].

  • CAS Number: 57808-66-9
  • MF: C22H24ClN5O2
  • MW: 425.911
  • Catalog: Dopamine Receptor
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 723.6±70.0 °C at 760 mmHg
  • Melting Point: 242.5ºC
  • Flash Point: 391.4±35.7 °C

(Rac)-VU 6008667

Rac-VU 6008667 is a selective negative allosteric modulator of muscarinic acetylcholine receptor subtype 5 (M5 NAM) with IC50s of 1.2 μM and 1.6 μM for human M5 and rat M5, respectively. Rac-VU 6008667 has high CNS penetration[1].

  • CAS Number: 2092917-63-8
  • MF: C24H17ClF2N2O2
  • MW: 438.85
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Fosnetupitant chloride monohydrochloride

Fosnetupitant chloride monohydrochloride (Pronetupitant chloride monohydrochloride) is an NK1 antagonist with pKi values of 9.5, 6.1 for human NK1 and NK3 receptor, respectively. Fosnetupitant chloride monohydrochloride is a methylene phosphate prodrug of Netupitant[1].

  • CAS Number: 1643757-72-5
  • MF: C31H37Cl2F6N4O5P
  • MW: 761.52
  • Catalog: Neurokinin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A