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 >
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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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Ro 10-5824 dihydrochloride

Ro 10-5824 dihydrochloride is a selective dopamine D4 receptor partial agonist, with Ki of 5.2 nM.

  • CAS Number: 189744-94-3
  • MF: C17H22Cl2N4
  • MW: 353.289
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Salbutamol-d9 acetate

Salbutamol-d9 (acetate) is the deuterium labeled Salbutamol[1]. Salbutamol is a short-acting β2-adrenergic receptor agonist used for the relief of bronchospasm in conditions such as asthma and chronic obstructive pulmonary disease (COPD).

  • CAS Number: 1781417-68-2
  • MF: C15H16D9NO5
  • MW: 308.42
  • Catalog: Adrenergic Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

RBC10

RBC10 is an anti-cancer agent. RBC10 inhibits the binding of Ral to its effector RALBP1. RBC10 also inhibits Ral-mediated cell spreading of murine embryonic fibroblasts and anchorage-independent growth of human cancer cell lines[1].

  • CAS Number: 362503-73-9
  • MF: C24H25ClN2O2
  • MW: 408.92
  • Catalog: Ras
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 616.3±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 326.5±31.5 °C

PNU 282987

PNU-282987 (free base) (Compound C7) is a potent α7 nicotinic acetylcholine receptor (nAChR) agonist with an EC50 of 154 nM. PNU-282987 (free base) is also a functional antagonist of the 5-HT3 receptor with an IC50 of 4541 nM[1].

  • CAS Number: 711085-63-1
  • MF: C14H17ClN2O
  • MW: 264.75
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Litoxetine

Litoxetine (SL 81.0385) is a selective 5-HT uptake inhibitor. Litoxetine is a 5-HT3 receptor antagonist with a Ki of 85 nM for cerebral 5-HT3 receptors. Litoxetine is an antidepressant and has antiemetic properties[1].

  • CAS Number: 86811-09-8
  • MF: C16H19NO
  • MW: 241.32800
  • Catalog: 5-HT Receptor
  • Density: 1.1g/cm3
  • Boiling Point: 387.1ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 159.2ºC

Basimglurant

Basimglurant (RG7090) is a potent, selective and orally available mGlu5 negative allosteric modulator with a Kd of 1.1 nM.

  • CAS Number: 802906-73-6
  • MF: C18H13ClFN3
  • MW: 325.767
  • Catalog: mGluR
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 526.6±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 272.3±32.9 °C

Chlorprothixene

Chlorprothixene has strong binding affinities to dopamine and histamine receptors, such as D1, D2, D3, D5, H1, 5-HT2, 5-HT6 and 5-HT7, with Ki of 18 nM, 2.96 nM, 4.56 nM, 9 nM, 3.75 nM, 9.4 nM, 3 nM and 5.6 nM, respectively.Target: Dopamine ReceptorChlorprothixene exerts strong binding affinities to the dopamine and histamine receptors, such as D1, D2, D3, D5 and H1 with Ki values of 18nM, 2.96 nM, 4.56 nM, 9 nM and 3.75 nM, respectively, but has little affinity to H3 (Ki >1000 nM) [1]. Chlorprothixene also shows high affinities for both rat 5-HT6 from stably transfected HEK-293 cells, and rat 5-HT7 receptors from transiently expressed COS-7 cells, with Ki values of 3 nM and 5.6 nM, respectively [2].Administration of Chlorprothixene restores normal ceramide concentrations in murine bronchial epithelial cells, reduces inflammation in the lungs of mice with cystic fibrosis (CF) and prevents infection with Pseudomonas aeruginosa, by inhibiting acidsphingomyelinase (Asm) and not neutral sphingomyelinase (Nsm) [3].

  • CAS Number: 113-59-7
  • MF: C18H18ClNS
  • MW: 315.860
  • Catalog: Dopamine Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 435.0±45.0 °C at 760 mmHg
  • Melting Point: 97-98°
  • Flash Point: 216.9±28.7 °C

Rotigotine Hydrochloride

Rotigotine Hydrochloride is a full agonist of dopamine receptor, a partial agonist of the 5-HT1A receptor, and an antagonist of the α2B-adrenergic receptor, with Ki of 0.71 nM, 4-15 nM, and 83 nM for the dopamine D3 receptor and D2, D5, D4 receptors, and dopamine D1 receptor.

  • CAS Number: 125572-93-2
  • MF: C19H26ClNOS
  • MW: 351.934
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: 470.1ºC at 760 mmHg
  • Melting Point: 186.5-187.5ºC
  • Flash Point: 238.1ºC

Talaglumetad hydrochloride

Talaglumetad hydrochloride is a prodrug of thetype II metabotropic glutamate receptor (mGluR2/3) agonist Eglumegad for the treatment of anxiety.

  • CAS Number: 441765-97-5
  • MF: C11H17ClN2O5
  • MW: 292.71600
  • Catalog: mGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DPCPX

DPCPX (PD 116948), a xanthine derivative, is a highly potent and selective Adenosine A1 receptor antagonist, with a Ki of 0.46 nM in 3H-CHA binding to A1 receptors in rat whole brain membranes[1][2][3].

  • CAS Number: 102146-07-6
  • MF: C16H24N4O2
  • MW: 304.38700
  • Catalog: Adenosine Receptor
  • Density: 1.195g/cm3
  • Boiling Point: 535.1ºC at 760mmHg
  • Melting Point: 178°C
  • Flash Point: 277.4ºC

3-Hydroxy agomelatine

3-Hydroxy agomelatine is a metabolite of Agomelatine. 3-Hydroxy agomelatine is a 5-HT2C receptor antagonist with an IC50 of 3.2 μM and a Ki of 1.8 μM[1].

  • CAS Number: 166526-99-4
  • MF: C15H17NO3
  • MW: 259.300
  • Catalog: 5-HT Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 545.8±40.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 283.9±27.3 °C

Loxiglumide

Loxiglumide is a cholecystokinin (CCK-1) receptor antagonist.

  • CAS Number: 107097-80-3
  • MF: C21H30Cl2N2O5
  • MW: 461.37900
  • Catalog: Cholecystokinin Receptor
  • Density: 1.233g/cm3
  • Boiling Point: 632.2ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 336.1ºC

MK-4256

MK-4256 is a potent and selective SSTR3 antagonist with IC50s of 0.66 nM and 0.36 nM in human and mouse receptor binding assays, respectively.

  • CAS Number: 1104599-69-0
  • MF: C27H23FN8O
  • MW: 494.523
  • Catalog: Somatostatin Receptor
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 826.7±75.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 453.8±37.1 °C

(R)-(-)-α-Methylhistamine dihydrobromide

(R)-(-)-α-Methylhistamine dihydrobromide is a potent and selective H3 histamine receptor agonist with a Kd of 50.3 nM[1][2]. (R)-(-)-α-Methylhistamine dihydrobromide can cross the blood-brain barrier, and can enhance memory retention, attenuates memory impairment in rats[3][4][5].

  • CAS Number: 868698-49-1
  • MF: C6H13Br2N3
  • MW: 206.08400
  • Catalog: Histamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Maropitant

Maropitant is a neurokinin (NK1) receptor antagonist. IC50 value:Target: NK1 receptorMaropitant is the first NK1 receptor antagonist developed to treat and prevent emesis in dogs. Treatment with 1 mg/kg Maropitant citrate, significantly reduced the size of ulcerative dermatitis (UD) lesions in mice. Intravenous Maropitant decreased (p < 0.05) MAC by 16% (1.74 ± 0.17%). In contrast, epidural administration of either saline or Maropitant did not change (p > 0.05) the MAC (2.17 ± 0.34% and 1.92 ± 0.12%, respectively).

  • CAS Number: 147116-67-4
  • MF: C32H40N2O
  • MW: 468.67300
  • Catalog: Neurokinin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

6-HYDROXYDOPAMINE HYDROBROMIDE

Oxidopamine hydrobromide is a selective catecholaminergic neurotoxin, depletes brain catecholamine levels via uptake and accumulation by a transport mechanism specific to these neurons. In vitro: Oxidopamine hydrobromide-induced apoptosis of PC12 cells was initiated by superoxide generation followed by caspase cascade activation, which was associated with the suppressed Akt phosphorylation and increased p38 phosphorylation. It is likely that pCPT-cAMP prevented the Oxidopamine hydrobromide-induced apoptosis via activation of the PI3-kinase/Akt pathway without any effect on superoxide generation or mitochondrial membrane depolarization. [1]In vivo the presence of sulfhydryl antioxidants protected against neuronal degeneration in the striatum, which was particularly remarkable in the case of CySH and was attributed to its capacity to remove the H2O2 produced in the autoxidation of Oxidopamine hydrobromide.

  • CAS Number: 636-00-0
  • MF: C8H12BrNO3
  • MW: 250.090
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: 406ºC at 760 mmHg
  • Melting Point: 216-220 °C(lit.)
  • Flash Point: 199.3ºC

Caerulein ammonium salt

Ceruletide, a biologically active decapeptide isolated from the skin of the Australian frog Hyla caerulea, is a potent cholecystokinetic agent, and acts as a cholecystokinin receptor agonist. Sequence: {pGlu}-Gln-Asp-Tyr(SO3H)-Thr-Gly-Trp-Met-Asp-Phe-NH2;{pGlu}-QD-Y(SO3H)-TGWMDF-NH2.

  • CAS Number: 17650-98-5
  • MF: C58H73N13O21S2
  • MW: 980.051
  • Catalog: Peptides
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: 224-226° (dec)
  • Flash Point: N/A

L-797591

L-797591 is a selective somatostatin receptor subtype 1 (SSTR1) agonist[1].

  • CAS Number: 217480-24-5
  • MF: C38H49N5O2
  • MW: 607.83
  • Catalog: Somatostatin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

KI-7

KI-7 is an A2B adenosine receptor positive allosteric modulator. KI-7 potentiates the cAMP accumulation induced by the non-selective A2B adenosine receptor agonist NECA (EC50=445.8 nM). KI-7 also potentiates the cAMP accumulation induced by the selective A2B adenosine receptor agonist BAY 60-6583 as well as by adenosine with EC50s of 2390 nM and 2550 nM, respectively[1][2].

  • CAS Number: 1489263-00-4
  • MF: C23H18N2O2
  • MW: 354.40
  • Catalog: Adenosine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Zavacorilant

Zavacorilant is capable of modulating glucocorticoid receptor (GR)[1].

  • CAS Number: 1781245-13-3
  • MF: C25H26FN7O3S2
  • MW: 555.65
  • Catalog: Glucocorticoid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SB-334867

SB-334867 is a selective non-peptide orexin OX1 receptor antagonist with a pKb value of 7.2.IC50 value: 7.2 (pKb) [1]Target: orexin OX1 receptor in vitro: SB-334867-A inhibited the orexin-A (10 nM) and orexin-B (100 nM)-induced calcium responses (pK(B)=7.27+/-0.04 and 7.23+/-0.03 respectively, n=8), but had no effect on the UTP (3 microM)-induced calcium response in CHO-OX(1) cells. SB-334867-A (10 microM) also inhibited OX(2) mediated calcium responses (32.7+/-1.9% versus orexin-A) [1].in vivo: Single-unit recordings in anesthetized rats demonstrated the central effects of the selective orexin-1 receptor antagonist SB-334867 (2 mg/kg, intravenous), as it reversed the excitatory effects of orexin-A administration (6 microg, intracerebroventricular) on the activity of locus coeruleus (LC) cells [2]. The ICV injection of SB-334867 alone had no effect on the formalin-induced nociceptive behaviors. Pre-treatment with SB-334867 at a dose of 0.5 nmol significantly attenuated the analgesia induced by morphine (at dose 1.5mg/kg of morphine; interphase and phase 2B and at dose 3mg/kg of morphine just phase 2B of formalin test) [3]. Administered alone, SB-334867 (30 mg/kg, but not lower doses) significantly reduced food intake and most active behaviours (eating, grooming, sniffing, locomotion and rearing), while increasing resting. Pretreatment with SB-334867 dose-dependently blocked these effects of orexin-A, with significant antagonism evident at dose levels (3-10 mg/kg) below those required to produce intrinsic behavioural effects under present test conditions in rats [4].Toxicity: Acute systemic treatment with the selective orexin-1 (OX1R) antagonist SB-334867 reduces food intake in rats, an effect associated with an acceleration in behavioural satiety and unrelated to gross behavioural disruption, alterations in palatability, or toxicity.

  • CAS Number: 249889-64-3
  • MF: C17H14ClN5O2
  • MW: 355.78
  • Catalog: Orexin Receptor (OX Receptor)
  • Density: 1.472g/cm3
  • Boiling Point: 450.5ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 226.2ºC

Brimonidine L-tartrate

UK 14,304 is a full α2-adrenergic receptor (α2-AR) agonist.Target: α2-adrenergic Receptor[3H]UK 14,034 is a full agonist at alpha 2-adrenergic receptors. [3H]UK 14,304 labels at least 2 specific binding sites in human brain that both have the characteristics of an alpha 2-adrenergic binding site. GTP decreases agonist binding at both of these sites, but with different potencies at each site [1-3].

  • CAS Number: 70359-46-5
  • MF: C15H16BrN5O6
  • MW: 442.221
  • Catalog: Adrenergic Receptor
  • Density: N/A
  • Boiling Point: 432.6ºC at 760 mmHg
  • Melting Point: 207-208ºC (dec.)
  • Flash Point: 215.4ºC

Atranorin

Atranorin is a lichen secondary metabolite. Atranorin inhibits lung cancer cell motility and tumorigenesis by affecting AP-1, Wnt, and STAT signaling and suppressing RhoGTPase activity[1][2].

  • CAS Number: 479-20-9
  • MF: C19H18O8
  • MW: 374.341
  • Catalog: Ras
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 535.7±50.0 °C at 760 mmHg
  • Melting Point: 156-158ºC
  • Flash Point: 189.3±23.6 °C

Ridaifen-B

Ridaifen-B (RID-B) is a potent antagonist of estrogen receptor α (ERα) with IC50 of 52.4 nM, a tamoxifen (HY-13757A) derivative[1]. Ridaifen-B is a high affinity, selective, inverse agonist at CB2 receptor (Ki=43.7 nM) over 17 folds CB1 receptor (Ki=732 nM). Ridaifen-B modulates G-protein (IC50=300 nM) and adenylyl cyclase activity with potency values predicted by CB2 affinity (IC50=134 nM). Ridaifen-B has anti-inflammatory, anti-cancer, and anti-osteoclastogenic effects[1][3].

  • CAS Number: 886465-70-9
  • MF: C34H42N2O2
  • MW: 510.70900
  • Catalog: Cannabinoid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NNC 26-9100

NNC 26-9100 is a selective somatostatin sst4 receptor full agonist (Ki: 6 nM, EC50: 2 nM). NNC 26-9100 decreases total soluble Aβ42, increases brain neprilysin activity and improves learning[1][2].

  • CAS Number: 199522-35-5
  • MF: C22H25BrCl2N6S
  • MW: 556.35
  • Catalog: Somatostatin Receptor
  • Density: 1.482g/cm3
  • Boiling Point: 731.167ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 395.996ºC

UNII:052RYF6JDD

Isoprenaline hemisulfate is a non-selective β-adrenergic receptor agonist with potent peripheral vasodilator, bronchodilator, and cardiac stimulating activities[1][2][3][4][5].

  • CAS Number: 299-95-6
  • MF: C22H36N2O10S
  • MW: 520.594
  • Catalog: Adrenergic Receptor
  • Density: N/A
  • Boiling Point: 417.5ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 179.7ºC

AF-DX 384

AF-DX 384 is a selective antagonist of M2 and M4 muscarinic acetylcholine receptors (Kis=6.03 and 10 nM, respectively)[1]. AF-DX 384 reverses deficits in novel object recognition and passive avoidance in aged rats, as well as in young rats with impairments induced by scopolamine[2].

  • CAS Number: 118290-26-9
  • MF: C27H38N6O2
  • MW: 478.630
  • Catalog: mAChR
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 618.4±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 327.8±31.5 °C

Gastrin I rat

Gastrin-1, rat (Rat Gastrin-17) is a peptide hormone, and can stimulate gastric acid secretion potently[1].

  • CAS Number: 81123-06-0
  • MF: C94H128N22O31S2
  • MW: 2126.28000
  • Catalog: Cholecystokinin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Setiptiline (maleate)

Setiptiline is a serotonin receptor antagonist.IC50 value:Target: 5-HT receptorSetiptiline is a tetracyclic antidepressant (TeCA) which acts as a noradrenergic and specific serotonergic antidepressant (NaSSA). Setiptiline acts as a norepinephrine reuptake inhibitor, α2-adrenergic receptor antagonist, and serotonin receptor antagonist, likely at the 5-HT2A, 5-HT2C, and/or 5-HT3 subtypes, as well as an H1 receptor inverse agonist/antihistamine. From Wikipedia.

  • CAS Number: 85650-57-3
  • MF: C23H23NO4
  • MW: 377.43300
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: 421.7ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 185.5ºC

TASP 0433864

A novel potent, selective mGluR2 positive allosteric modulator with EC50 of 199 and 206 nM for human and rat mGlu2, respectively, without exerting agonist activity; has negligible activities for other mGlu receptors, including mGlu3 receptor; potentiates the mGlu2 receptor-mediated presynaptic inhibition of glutamate release, inhibits both MK-801- and ketamine-increased cortical γ band oscillation in the rat cortical electroencephalogram; significantly inhibits both ketamine- and methamphetamine-increased locomotor activities in mice.

  • CAS Number: 1431980-60-7
  • MF: C18H23N3O3
  • MW: 329.393
  • Catalog: mGluR
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 521.4±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 269.1±32.9 °C