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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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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Leumorphin, human

Leumorphin, human is a potent kappa opioid receptor (κ opioid receptor) agonist. Leumorphin, human inhibits the contraction of the myenteric plexus-longitudinal muscle preparation of the guinea pig ileum[1].

  • CAS Number: 88846-98-4
  • MF: C150H224N42O46
  • MW: 3351.64
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Jatrorrhizinehydroxide

Jatrorrhizine hydroxide is an alkaloid isolated from Coptis chinensis with neuroprotective, antimicrobial, antiplasmodial and antioxidant activities[1]. Jatrorrhizine hydroxide is a potent and orally active inhibitor of AChE (IC50=872 nM) over >115-fold selectivity for BuChE[2]. Jatrorrhizine hydroxide reduces uptake of serotonin (5-HT) and norepinephrine (NE) via inhibition of uptake-2 transporters[3].

  • CAS Number: 483-43-2
  • MF: C20H21NO5
  • MW: 355.38
  • Catalog: Bacterial
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

R-121919

R121919 is a potent small-molecule CRF1 receptor antagonist with a Ki of 2 to 5 nM for the CRF1 receptor and over 1000-fold weaker activity at the CRF2 receptor, CRF-binding protein, or 70 other receptor types.

  • CAS Number: 195055-03-9
  • MF: C22H32N6
  • MW: 380.53000
  • Catalog: CRFR
  • Density: 1.114g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

KRAS G12C inhibitor 42

KRAS G12C inhibitor 42 is a potent inhibitor of KRAS G12C. The Ras family of proteins is an important intracellular signaling molecule that plays an important role in growth and development. KRAS G12C inhibitor 42 has the potential for the research of KRAS G12C-mediated cancer (extracted from patent WO2020146613A1, compound 10)[1].

  • CAS Number: 2454488-02-7
  • MF: C33H34FN7O2
  • MW: 579.67
  • Catalog: Ras
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Emraclidine

Emraclidine is a muscarinic M4 receptor positive allosteric modulator (WO2018002760, compound 11). Emraclidine can be used for the research of neurological diseases[1].

  • CAS Number: 2170722-84-4
  • MF: C20H21F3N4O
  • MW: 390.40
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

diphenylpyraline

Diphenylpyraline is a potent histamine H1 receptor antagonist. Diphenylpyraline acts as an orally active antihistamine agent with antimuscarinic and antiallergic effects. Diphenylpyraline can be used for the research of allergic diseases, including rhinitis and hay fever, and pruritic skin disorders et.al[1].

  • CAS Number: 147-20-6
  • MF: C19H23NO
  • MW: 281.39200
  • Catalog: Histamine Receptor
  • Density: 1.08 g/cm3
  • Boiling Point: 378.7ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 111.6ºC

TCS-OX2-29

TCS-OX2-29 is a potent and selective OX2 receptor antagonist with IC50 of 40 nM. Displays >250-fold selectivity for OX2 over OX1.target: OX2 IC 50: 40 nMIn vitro:TCS-OX2-29 shows selectivity for ion channels, and transporters (<30% inhibition at 10 μM), which includes G-protein coupled receptors associated with food intake including galanin and neuripeptide Y. [1]TCS-OX2-29 Inhibits orexin A induced IP3 accumulation and ERK1/2 phosphorylation in CHO cells transfected with the OX2 receptor. [2]

  • CAS Number: 372523-75-6
  • MF: C23H31N3O3
  • MW: 397.51
  • Catalog: Orexin Receptor (OX Receptor)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

VU0467154

VU0467154 is a positive allosteric modulator of the M4 muscarinic acetylcholine receptor (mAChR), potentiating the response to ACh with pEC50s of 7.75, 6.2 and 6 for rat, human and cynomolgus monkey M4 receptor, respectively.

  • CAS Number: 1451993-15-9
  • MF: C17H15F3N4O3S2
  • MW: 444.45100
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Triprolidine hydrochloride

Triprolidine is an oral active, first-generation histamine H1-receptor antagonist. Triprolidine can be used for the research of allergic rhinitis. triprolidine exhibits spinal motor and sensory block in rats[1][2][3].

  • CAS Number: 550-70-9
  • MF: C19H23ClN2
  • MW: 314.85200
  • Catalog: Histamine Receptor
  • Density: 1.061g/cm3
  • Boiling Point: 435.4ºC at 760mmHg
  • Melting Point: 59-61ºC
  • Flash Point: 217.1ºC

Cyclopentolate Hydrochloride

Cyclopentolate (DL-Cyclopentolate) hydrochloride is an anti-muscarinic agent commonly used in the ophthalmologic practice. Cyclopentolate hydrochloride is an Atropine-like muscarinic receptors antagonist with a pKB value of 7.8 (on the circular ciliary muscle)[1][2].

  • CAS Number: 5870-29-1
  • MF: C17H26ClNO3
  • MW: 327.84600
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: 409.7ºC at 760mmHg
  • Melting Point: 137-141°
  • Flash Point: 201.5ºC

GSK3004774

GSK3004774 is a potent, nonabsorbable agonist of CaSR, with an pEC50 of 7.3, 6.6 and 6.5 for human, mouse and rat CaSR, respectively. GSK3004774 shows an EC50 of 50 nM for human CaSR[1].

  • CAS Number: 2138814-32-9
  • MF: C32H40N4O3
  • MW: 528.69
  • Catalog: CaSR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Aligeron

Aligeron is a non-selective prostaglandin (PG) antagonist, and has vasodilatory properties.

  • CAS Number: 70713-45-0
  • MF: C20H24N2
  • MW: 292.41800
  • Catalog: Prostaglandin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Imnopitant

Imnopitant is a NK1 receptor antagonist (WO2020132716, compound 1) [1].

  • CAS Number: 290297-57-3
  • MF: C28H28F6N4O
  • MW: 550.54
  • Catalog: Neurokinin Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 606.5±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 320.6±31.5 °C

Fenoldopam (mesylate)

Fenoldopam(SKF 82526) mesylate is a drug and synthetic benzazepine derivative which acts as a selective D1 receptor partial agonist.Target: D1 ReceptorFenoldopam is a selective dopamine-1 (DA1) agonist with natriuretic/diuretic properties. Fenoldopam stimulated cAMP accumulation in LLC-PK1 cells in a dose-dependent manner, an effect which could be blocked by the DA1-selective antagonist Sch 23390. Although fenoldopam was more potent than DA (EC50 55.5 +/- 7.75 nM vs. 1.65 +/- 0.64 microM) in stimulating cAMP accumulation in LLC-PK1 cells, the maximum stimulation obtained by fenoldopam was only 37% of the maximum stimulation obtained by DA(Emax 13.0 +/- 2.95 pmol/mg of protein vs. 35.6 +/- 10.19 pmol/mg of protein) [1]. Fenoldopam is a selective dopamine1 (DA1) receptor agonist. Most of the DA1 receptor agonist activity of fenoldopam resides in the R-enantiomer, which also shows weaker alpha 2-adrenoceptor antagonist activity Fenoldopam produces vasodilation in vascular beds that are rich in vascular DA1 receptors [2].

  • CAS Number: 67227-57-0
  • MF: C17H20ClNO6S
  • MW: 401.86
  • Catalog: Dopamine Receptor
  • Density: 1.38g/cm3
  • Boiling Point: 522.6ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 269.9ºC

Isoferulic acid

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[1].trans-isoferulic acid suppresses NO and PGE2 production through the induction of Nrf2-dependent heme oxygenase-1 (HO-1)[2].

  • CAS Number: 25522-33-2
  • MF: C10H10O4
  • MW: 194.184
  • Catalog: Prostaglandin Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 410.2±35.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 167.6±19.4 °C

Befiradol

Befiradol (F13640) is a selective 5-HT1A receptor agonist.

  • CAS Number: 208110-64-9
  • MF: C20H22ClF2N3O
  • MW: 393.85800
  • Catalog: 5-HT Receptor
  • Density: 1.3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Grifolic acid

Grifolic acid is a phenolic compound that is first extracted from the mushroom Albatrellus confluens. Grifolic acid acts as an agonist of the free fatty acid receptor (FFAR4/GPR120)[1].

  • CAS Number: 80557-12-6
  • MF: C23H32O4
  • MW: 372.498
  • Catalog: GPR120
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 557.1±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 304.8±26.6 °C

Naronapride

Naronapride (ATI-7505) is a potent prokinetic 5-HT4 receptor agonist. Naronapride can be used for gastrointestinal diseases research[1].

  • CAS Number: 860174-12-5
  • MF: C27H41ClN4O5
  • MW: 537.09100
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Terbogrel

Terbogrel is an orally available thromboxane A2 receptor antagonist and a thromboxane A2 synthase inhibitor, with both IC50s of about 10 nM.

  • CAS Number: 149979-74-8
  • MF: C23H27N5O2
  • MW: 405.49300
  • Catalog: Prostaglandin Receptor
  • Density: 1.13g/cm3
  • Boiling Point: 601.3ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 317.4ºC

Carebastine

Carebastine is the active metabolite of Ebastine. Carebastine is a histamine H1 receptor antagonist. Carebastine inhibits VEGF-induced HUVEC and HPAEC proliferation, migration and angiogenesis in a dose-dependent manner[1]. Carebastine suppresses the expression of macrophage migration inhibitory factor[2].

  • CAS Number: 90729-42-3
  • MF: C32H37NO4
  • MW: 499.641
  • Catalog: Histamine Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 657.9±55.0 °C at 760 mmHg
  • Melting Point: 178-180ºC
  • Flash Point: 351.7±31.5 °C

Palosuran

Palosuran (ACT-058362) is a new potent and specific antagonist of the human UT receptor with an IC50 of 3.6±0.2 nM. IC50 Value: 3.6±0.2 nM [1]Target: Urotensin Receptor (GPR14)in vitro: Palosuran inhibited 125I-U-II binding to human UT receptors in membrane preparations from CHO cells carrying the human UT receptors almost as potently as cold U-II, with an IC50 of 3.6 ± 0.2 nM. On cells, the inhibitory binding potency of palosuran against human UT receptor was lower than on membranes (IC50 = 46.2 ± 13 nM on TE 671 cells and 86 ± 30 nM on recombinant CHO cells). Compared with the human UT receptor, the binding inhibitory potency of palosuran against the rat UT receptor was lower in membrane preparation (400-fold), as well as in cells (>120-fold) [1].in vivo: Long-term treatment of streptozotocin-induced diabetic rats with palosuran improved survival, increased insulin, and slowed the increase in glycemia, glycosylated hemoglobin, and serum lipids. Furthermore, palosuran increased renal blood flow and delayed the development of proteinuria and renal damage [2]. Palosuran was rapidly absorbed with maximum plasma concentrations at 1 hour after drug administration. The accumulation factor was 1.7 (geometric mean) (95% confidence interval, 1.3 to 2.1).Palosuran was well tolerated [3]. In mesenteric vessels, palosuran treatment up-regulated expression of RhoA and Rho-kinase, increased Rho-kinase-activity, and diminished nitric oxide (NO)/cyclic guanosine 3',5'-monophosphate (cGMP) signaling. Moreover, palosuran increased renal blood flow, sodium, and water excretion in BDL rats [4].Toxicity: Palosuran was well tolerated. No serious adverse events or dose-related adverse events were reported. No treatment-related pattern was detected for vital signs, clinical laboratory parameters, or electrocardiography parameters [5].

  • CAS Number: 540769-28-6
  • MF: C25H30N4O2
  • MW: 418.53100
  • Catalog: Urotensin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Alamandine

Alamandine, a member of the renin-angiotensin system (RAS), a vasoactive peptide, is an endogenous ligand of the G protein-coupled receptor MrgD. Alamandine targets to protect the kidney and heart through anti-hypertensive actions[1][2].

  • CAS Number: 1176306-10-7
  • MF: C40H62N12O9
  • MW: 854.995
  • Catalog: Angiotensin Receptor
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

KRAS G12C inhibitor 56

KRAS G12C inhibitor 56 (compound IC-6) is a potent SOS1 inhibitor with an IC50 of 1.6 nM. KRAS G12C inhibitor 56 can be used in cancer research[1].

  • CAS Number: 2749963-77-5
  • MF: C32H39N7O4S
  • MW: 617.76
  • Catalog: Ras
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Istradefylline-13C,d3

Istradefylline-13C,d3 is the 13C- and deuterium labeled. Istradefylline is a very potent, selective and orally active adenosine A2A receptor antagonist with Ki of 2.2 nM in experimental models of Parkinson's disease.

  • CAS Number: 2749234-46-4
  • MF: C1913CH21D3N4O4
  • MW: 388.44
  • Catalog: Adenosine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PF-04634817

PF-0463481, an oral CCR2/5 dual antagonist, with a favorable ocular safety profile versus intravitreal therapies[1]. PF-0463481 is safe and well-tolerated and being developed for the treatment of diabetic nephropathy[2].

  • CAS Number: 1228111-63-4
  • MF: C25H36F3N5O3
  • MW: 511.58
  • Catalog: CCR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MM 419447

MM 419447, a linaclotide metabolite, is a guanylate cyclase-C agonist. MM 419447 has the potential for the research of the irritable bowel syndrome with constipation (IBS-C)[1].

  • CAS Number: 1092457-78-7
  • MF: C50H70N14O19S6
  • MW: 1363.56
  • Catalog: Guanylate Cyclase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GR 203040

GR203040 is an orally active NK1 receptor antagonist with a pKi of 10.3. GR203040 shows potent antiemetic activity[1].

  • CAS Number: 168398-02-5
  • MF: C20H26Cl2N6O
  • MW: 437.37
  • Catalog: Neurokinin Receptor
  • Density: N/A
  • Boiling Point: 560.4ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 292.7ºC

Emedastine

Emedastine is an orally active, selective and high affinity histamine H1 receptor antagonist with a Ki value of 1.3 nM. Emedastine is a benzimidazole derivative with potent antiallergic properties and used for allergic rhinitis, allergic skin diseases and allergic conjunctivitis[1][2][3].

  • CAS Number: 87233-61-2
  • MF: C17H26N4O
  • MW: 302.414
  • Catalog: Histamine Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 446.6±55.0 °C at 760 mmHg
  • Melting Point: 148-151ºC
  • Flash Point: 223.9±31.5 °C

GLP-1R modulator L7-028

GLP-1R modulator L7-028 is an allosteric modulator enhancing GLP-1 binding to GLP-1R via a transmembrane site (EC50 11.01 ± 2.73 μM).

  • CAS Number: 2648317-95-5
  • MF: C24H28N2O3
  • MW: 392.49
  • Catalog: Glucagon Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Agomelatine

Agomelatine is a competitive antagonist of human and porcine serotonin (5-HT2C) receptors (pKi = 6.2 and 6.4, respectively) as well as human 5-HT2B receptors (pKi = 6.6). IC50 value: 6.2 (pKi, 5-HT2c); 6.6 (pKi, 5-HT2b)Target: 5-HT2C Receptor; 5-HT2B receptorIt is classified as a norepinephrine-dopamine disinhibitor (NDDI) due to its antagonism of the 5-HT2C receptor. Activation of 5-HT2C receptors by serotonin inhibits dopamine and norepinephrine release. Antagonism of 5-HT2C results in an enhancement of DA and NE release and activity of frontocortical dopaminergic and adrenergic pathways. Agomelatine is also a potent agonist at melatonin receptors which makes it the first melatonergic antidepressant. Agomelatine is an antidepressant drug.

  • CAS Number: 138112-76-2
  • MF: C15H17NO2
  • MW: 243.301
  • Catalog: 5-HT Receptor
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 478.8±28.0 °C at 760 mmHg
  • Melting Point: 107-109ºC
  • Flash Point: 243.4±24.0 °C