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 >
ADC Cytotoxin ADC Linker Drug-Linker Conjugates for ADC PROTAC-linker Conjugate for PAC
Apoptosis >
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Autophagy >
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Cytoskeleton >
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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
Neuronal Signaling >
5-HT Receptor AChE Adenosine Kinase Amyloid-β Beta-secretase CaMK CGRP Receptor COMT Dopamine Receptor Dopamine Transporter FAAH GABA Receptor GlyT iGluR Imidazoline Receptor mAChR Melatonin Receptor Monoamine Oxidase nAChR Neurokinin Receptor Opioid Receptor Serotonin Transporter γ-secretase
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propiomazine

Propiomazine is an orally active antihistamine agent with sedative effects. Propiomazine can be used in the research of insomnia[1][2].

  • CAS Number: 362-29-8
  • MF: C20H24N2OS
  • MW: 340.48200
  • Catalog: Histamine Receptor
  • Density: 1.137g/cm3
  • Boiling Point: 500.8ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 256.7ºC

K-Ras(G12C) inhibitor 9

K-Ras (G12C) inhibitor 9 is an allosteric inhibitor of the K-Ras (G12C)[1].

  • CAS Number: 1469337-91-4
  • MF: C16H21ClIN3O4S
  • MW: 513.77800
  • Catalog: Ras
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ataciguat

Ataciguat (HMR-1766) is a nitric oxide-independent soluble guanylate cyclase (sGC) activator. Ataciguat is able to activate the ferric heme-iron redox form of sGC that stimulate the production of cyclic GMP (cGMP). Ataciguat exhibits vasodilator effects[1][2][3].

  • CAS Number: 254877-67-3
  • MF: C21H19Cl2N3O6S3
  • MW: 576.493
  • Catalog: Guanylate Cyclase
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

[Des-Arg9]-Bradykinin acetate

[Des-Arg9]-Bradykinin acetate is a Bradykinin B1 receptor agonist that displays selectivity for B1 over B2 receptors.

  • CAS Number: 23827-91-0
  • MF: C46H65N11O12
  • MW: 964.07
  • Catalog: Peptides
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Irsogladine

Irsogladine is a PDE4 inhibitor and muscarinic acetylcholine receptor binder.Target: PDE4; mACHRIrsogladine treatment (300 and 500 mg/kg/day) resulted in a dose-dependent reduction of angiogenesis in wild-type mice by 21 and 45.3% (P < 0.02, P < 0.001), in tPA-deficient mice by 42.6 and 46% (P < 0.001, P < 0.001), and in uPA-deficient mice by 27.2 and 46% (P < 0.05, p < 0.001), respectively. Irsogladine inhibits bFGF-induced angiogenesis in wild-type, tPA-knockout, and uPA-knockout mice [1]. Irsogladine up-regulates GJIC between PC cells via regulation of the PKA pathway. It also suggests a useful adjuvant of Irsogladine to pancreatic cancer therapy [2]. irsogladine produces the increase of intracellular cAMP content via non-selective inhibition of PDE isozymes, which may be a key mechanism involved in its gastroprotective actions [3].

  • CAS Number: 57381-26-7
  • MF: C9H7Cl2N5
  • MW: 256.091
  • Catalog: mAChR
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 552.2±60.0 °C at 760 mmHg
  • Melting Point: 268-269°C
  • Flash Point: 287.8±32.9 °C

Proxyphylline

Proxyphylline is a methylxanthine derivative clinical used as cardiac stimulant, vasodilator and bronchodilator.

  • CAS Number: 603-00-9
  • MF: C10H14N4O3
  • MW: 238.24300
  • Catalog: Adenosine Receptor
  • Density: 1.46 g/cm3
  • Boiling Point: 487.2ºC
  • Melting Point: 134-136ºC
  • Flash Point: 248.5ºC

U-75302

U-75302 is a potent inhibitor of leukotriene B4. U-75302 is a pyridine analogue. U-75302 has the potential for the research of inflammatory diseases[1].

  • CAS Number: 119477-85-9
  • MF: C22H35NO3
  • MW: 361.52
  • Catalog: Leukotriene Receptor
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 567.2±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 296.8±30.1 °C

Biotin-Substance P

Biotin-Substance P is the biotin tagged Substance P. Substance P (Neurokinin P) is a neuropeptide, acting as a neurotransmitter and as a neuromodulator in the CNS. The endogenous receptor for substance P is neurokinin 1 receptor (NK1-receptor, NK1R)[1].

  • CAS Number: 87468-58-4
  • MF: C73H112N20O15S2
  • MW: 1573.93000
  • Catalog: Neurokinin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Alvimopan (monohydrate)

Alvimopan monohydrate is a peripherally acting mu-opioid receptor (PAM-OR, IC50= 1.7 nM) antagonist for accelerating gastrointestinal recovery after surgery. IC50 Value: 1.7 nM (Mu-type opioid receptor) [1]in vitro: The dissociation rate of alvimopan from the micro opioid receptor (t(1/2)=30--44 min) was comparable to that of the long acting partial agonist buprenorphine (t(1/2)=44 min), but was slower than those of the antagonists naloxone (t(1/2)=0.82 min) and N-methylnaltrexone (t(1/2)=0.46 min) [2].in vivo: Alvimopan did not significantly accelerate GI-3 compared with placebo [6 mg: hazard ratio (HR) = 1.20, p = 0.080; 12 mg: HR = 1.24, p = 0.038). However, after adjustment for significant covariates (sex/surgical duration), benefits were significant for both doses (6 mg: HR = 1.24, p = 0.037; 12 mg: HR = 1.26, p = 0.028). Alvimopan also significantly accelerated time to GI-2 (6 mg: HR = 1.37, p = 0.008; 12 mg: HR = 1.33, p = 0.018) and DCO (6 mg: HR = 1.31, p = 0.008; 12 mg: HR = 1.28, p = 0.015) [3]. Alvimopan (1 and 3 mg/kg) significantly reversed this delayed GI transit when administered 45 min prior to surgery. However, the effects of alvimopan were less pronounced when administered following surgery [4].Toxicity:The most common treatment-emergent adverse events across all treatment groups were nausea, vomiting, and hypotension; the incidence of nausea and vomiting was reduced by 53 percent in thealvimopan 12-mg group [5].Clinical trial: Intercostal Nerve Block With Liposome Bupivacaine in Subjects Undergoing Posterolateral Thoracotomy. Phase 3

  • CAS Number: 1383577-62-5
  • MF: C25H34N2O5
  • MW: 442.54800
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Uridine 5′-diphosphoglucose-13C disodium

Uridine 5′-diphosphoglucose-13C disodium is the 13C labeled Uridine 5′-diphosphoglucose disodium salt. Uridine 5′-diphosphoglucose disodium salt (UDP-D-Glucose disodium salt) is the precursor of glucose-containing oligosaccharides, polysaccharides, glycop

  • CAS Number: 478529-38-3
  • MF: C15H22N2Na2O17P2
  • MW: 611.25800
  • Catalog: P2Y Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Acifran

Acifran (AY 25712), an antihyperlipidemic agent, is an orally active agonist of GPR109A (HM74A) and GPR109B, the high and low affinity receptors for Niacin[1][2].

  • CAS Number: 72420-38-3
  • MF: C12H10O4
  • MW: 218.20500
  • Catalog: GPR109A
  • Density: 1.343 g/cm3
  • Boiling Point: 378.4ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 149.4ºC

CB1 antagonist 1

CB1 antagonist 1 is an antagonist of CB1 receptor, used in the research of metabolic syndrome and obesity, neuroinflammatory disorders, cognitive disorders and psychosis, gastrointestinal disorders, and cardiovascular conditions.

  • CAS Number: 890037-68-0
  • MF: C26H22Cl2N4
  • MW: 461.39
  • Catalog: Cannabinoid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

6'-GNTI dihydrochloride

6'-GNTI dihydrochloride, a κ-opioid receptor (KOR) agonist, displays bias toward the activation of G protein-mediated signaling over β-arrestin2 recruitment. 6'-GNTI 6'-GNTI dihydrochloride only activates the Akt pathway in striatal neurons[1].

  • CAS Number: 2410327-94-3
  • MF: C27H31Cl2N5O3
  • MW: 544.47
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CYM 5520

CYM-5520 is a selective and allosteric sphingosine 1-phosphate receptor 2 (S1PR2) agonist with an EC50 of 480 nM. CYM-5520 does not activate S1PR1, S1PR3, S1PR4 and S1PR5 receptors. CYM-5520 can co-bind in the S1PR2 receptor with S1P. CYM-5520 can be used for osteoporosis research[1][2].

  • CAS Number: 1449747-00-5
  • MF: C21H19N3O2
  • MW: 345.395
  • Catalog: LPL Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 580.5±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 304.9±30.1 °C

Macimorelin Acetate

Macimorelin (EP-1572), a GH secretagogue, is an orally active GHSR agonist. Macimorelin stimulates GH release. Macimorelin can be used in the research of adult growth hormone deficiency (AGHD), and Cancer anorexia-cachexia syndrome (CACS)[1][2][3].

  • CAS Number: 381231-18-1
  • MF: C26H30N6O3
  • MW: 474.555
  • Catalog: GHSR
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 948.6±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 527.5±34.3 °C

S1P1 agonist 4

S1P1 agonist 4 has a better profile in both potency (EC50 < 0.05 mg/kg) and predicted human half-life (t1/2 ∼ 5 days).

  • CAS Number: 1883345-11-6
  • MF: C24H31NO3
  • MW: 381.51
  • Catalog: LPL Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Peptide YY (13-36) (canine, mouse, porcine, rat) trifluoroacetate salt

Peptide YY (13-36) (canine, mouse, porcine, rat) is a Y2 receptor subtype agonist[1].

  • CAS Number: 86895-09-2
  • MF: C135H209N41O38
  • MW: 3014.36
  • Catalog: Neuropeptide Y Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Agmatine sulfate

Agmatine sulfate exerts modulatory action at multiple molecular targets, such as neurotransmitter systems, ion channels and nitric oxide synthesis. It is an endogenous agonist at imidazoline receptor and a NO synthase inhibitor.

  • CAS Number: 2482-00-0
  • MF: C5H16N4O4S
  • MW: 228.270
  • Catalog: Imidazoline Receptor
  • Density: N/A
  • Boiling Point: 281.4ºC at 760 mmHg
  • Melting Point: 234-238 °C(lit.)
  • Flash Point: 124ºC

D2343

D2343 is a β2-adrenoceptor agonist and also is an α1- adrenoceptor inhibitor.

  • CAS Number: 72734-63-5
  • MF: C20H27NO3
  • MW: 329.43300
  • Catalog: Adrenergic Receptor
  • Density: 1.116g/cm3
  • Boiling Point: 506.8ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 260.3ºC

PROTAC KRAS G12C degrader-2

PROTAC KRAS G12C degrader-2 (compound 432) is a modulator of K-Ras protein hydrolysis. PROTAC KRAS G12C degrader-2 is a bifunctional compound, which contain on one end a cereblon inhibitor of apoptosis proteins (IAP) and on the other end a moiety which binds KRAS[1].

  • CAS Number: 2378257-72-6
  • MF: C51H53ClFN9O7
  • MW: 958.47
  • Catalog: Ras
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Naloxone benzoylhydrazone

Naloxone benzoylhydrazone (NalBzoH) is a mixed agonist/antagonist. Naloxone benzoylhydrazone is a prototypic κ3-opioid receptor agonist, and a partial agonist at the cloned μ and δ opioid receptors, and an antagonist at opioid-like NOP receptors. Naloxone benzoylhydrazone has potently analgesia effect[1][2][3].

  • CAS Number: 119630-94-3
  • MF: C26H27N3O4
  • MW: 445.51000
  • Catalog: Opioid Receptor
  • Density: 1.44g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Digeranyl bisphophonate

Digeranyl bisphophonate is a potent geranylgeranylpyrophosphate (GGPP) synthase inhibitor, which inhibits geranylgeranylation of Rac1.

  • CAS Number: 878143-03-4
  • MF: C21H34Na4O6P2
  • MW: 536.4
  • Catalog: Ras
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(Rac)-E1R

(Rac)-E1R (Compound 2) is the racemate of E1R. (Rac)-E1R is a sigma-1 receptor positive allosteric modulator (Sig1R PAM) for the treatment of cognition/memory disorders[1].

  • CAS Number: 787623-60-3
  • MF: C13H16N2O2
  • MW: 232.28
  • Catalog: Sigma Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GSK163090

GSK163090 is a potent, selective, and orally active 5-HT1A/B/D receptor antagonist with pKi of 9.4/8.5/9.7, and 6.3/6.7 for 5-HT1A/B/D, and dopamine D2/D3, respectively.IC50 value: 9.4/8.5/9.7 (pKi) [1]Target: 5-HT in vitro: GSK163090 demonstrates clear dose-dependent inhibition of the 8-OH-DPAT-induced hyperlocomotor activity (hLMA), with ED50 values ranging from 0.03 to 1 mg/kg. GSK163090 was devoid of agonist activity at R1 receptors, but rather it demonstrated amoderate functional antagonismof the phenylephrineinduced contraction of rabbit aorta (pIC50=6.9). [1]in vivo: Fromamong these analogues, the cyclic urea derivative, GSK163090, emerged due to its low hERG affinity and excellent in vitro DMPK profile. The superior quality of GSK163090 was further highlighted by its commendable in vivo pharmacokineticprofile in rat and its outstanding activity in the 5-HT1A PD model, where 50% efficacy was achieved at a blood concentration of 3 ng/mL. On the basis of these results and its promising preclinical developability profile, GSK163090 was selected as an appropriate development candidate for progression toward clinical proof-of-concept studies. [1]

  • CAS Number: 844903-58-8
  • MF: C25H29N5O
  • MW: 415.531
  • Catalog: 5-HT Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

[DAla2, DArg6] Dynorphin A, (1-13) (porcine)

[DAla2, DArg6] Dynorphin A, (1-13) (porcine) (DADAD) is an opioid peptide (dynorphinl-13, DYN) derivative found in porcine pituitary extracts. DYN is highly potent at the peripheral opioid receptors GPI and MVD, but is readily and rapidly degraded in vivo. [DAla2, DArg6] Dynorphin A, (1-13) (porcine) has some resistance to enzymatic cleavage and prevents peptide cleavage by enzymes[1].

  • CAS Number: 75921-88-9
  • MF: C76H128N24O15
  • MW: 1617.98
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Setipiprant

Setipiprant is an orally available, selective CRTH2 antagonist. CRTH2 is a G protein-coupled receptor for PGD2.IC50 value: 6.0 nMTarget: PGD2in vitro: Setipiprant is an orally available, selective CRTH2 (chemoattractant receptor-homologous molecule expressed on T helper [Th]-2 cells) antagonist. CRTH2 is a G protein-coupled receptor for prostaglandin (PGD2). PGD2 is produced by the mast cells and is a key mediator in various inflammatory diseases, including allergy and asthma. Binding of PGD2 to CRTH2, which are expressed on the surface of blood-borne cells, induces chemotaxis of Th2 cells, basophils, and eosinophils, and stimulates cytokine release from these cells. Thus, antagonism of CRTH2 receptors is considered to be a promising therapeutic target for various allergic diseases and asthma.

  • CAS Number: 866460-33-5
  • MF: C24H19FN2O3
  • MW: 402.418
  • Catalog: Prostaglandin Receptor
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 690.4±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 371.4±31.5 °C

Pentiapine

Pentiapine is a novel dopamine release inhibitor.

  • CAS Number: 81382-51-6
  • MF: C15H17N5S
  • MW: 299.39400
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Butoxamine hydrochloride

Butaxamine (Butoxamin) hydrochloride is a specific β2-adrenergic receptor blocker. Butaxamine hydrochloride inhibits the decreases in urine volume in ethanol-anesthetized, water-diuretic rats[1].

  • CAS Number: 5696-15-1
  • MF: C15H26ClNO3
  • MW: 303.82500
  • Catalog: Adrenergic Receptor
  • Density: N/A
  • Boiling Point: 391ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 190.3ºC

Pirolate

Pirolate is a histamine H1 receptor.

  • CAS Number: 55149-05-8
  • MF: C16H15N3O5
  • MW: 329.30700
  • Catalog: Histamine Receptor
  • Density: 1.43g/cm3
  • Boiling Point: 518.8ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 267.5ºC

Evocalcet

Evocalcet has an activating effect on calcium sensing receptor (CaSR) extracted from patent WO 2017061621 A1, compound A.

  • CAS Number: 870964-67-3
  • MF: C24H26N2O2
  • MW: 374.475
  • Catalog: CaSR
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 594.4±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 313.3±30.1 °C