Neuronal Signaling is involved in the regulation of the mechanics of the central nervous system such as its structure, function, genetics and physiology as well as how this can be applied to understand diseases of the nervous system. Every information processing system in the CNS is composed of neurons and glia, neurons have evolved unique capabilities for intracellular signaling (communication within the cell) and intercellular signaling (communication between cells).

G protein-coupled receptors (GPCRs), including 5-HT receptor, histamine receptor, opioid receptor, and etc, are the largest class of sensory proteins and are important therapeutic targets in Neuronal Signaling. GPCRs are activated by diverse stimuli, including light, enzymatic processing of their N-termini, and binding of proteins, peptides, or small molecules such as neurotransmitters, and regulate neuronal excitability by indirectly modulating the function of voltage-gated channels, such as voltage-gated calcium channel and transient receptor potential (TRP) ion channels. Besides, Notch signaling, such as β- and γ-secretase, also plays multiple roles in the development of the CNS including regulating neural stem cell (NSC) proliferation, survival, self-renewal and differentiation.

GPCR dysfunction caused by receptor mutations and environmental challenges contributes to many neurological diseases. Notch signaling in neurons, glia, and NSCs is also involved in pathological changes that occur in disorders such as stroke, Alzheimer's disease and CNS tumors. Thus, targeting Neuronal Signaling, such as notch signaling and GPCRs, can be used as therapeutic interventions for several different CNS disorders.

References:
[1] Lathia JD, et al. J Neurochem. 2008 Dec;107(6):1471-81.
[2] Palczewski K, et al. Annu Rev Neurosci. 2013 Jul 8;36:139-64.
[3] Geppetti P, et al. Neuron. 2015 Nov 18;88(4):635-49.


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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AT-121 hydrochloride

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

  • CAS Number: 2099681-71-5
  • MF: C24H39ClN4O3S
  • MW: 499.11
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DM 235

Sunifiram (DM-235) is a piperazine derived ampakine-like drug which has nootropic effects in animal studies with significantly higher potency than piracetam.IC50 value: Target: in vitro: DM 232 and DM 235 are novel antiamnesic compounds structurally related to ampakines. The involvement of AMPA receptors in the mechanism of action of DM 232 and DM 235 was, therefore, investigated in vivo and in vitro. Both compounds (0.1 mg/kg i.p.) were able to reverse the amnesia induced by the AMPA receptor antagonist NBQX (30 mg/kg i.p.) in the mouse passive avoidance test. At the effective doses, the investigated compounds did not impair motor coordination, as revealed by the rota rod test, nor modify spontaneous motility and inspection activity, as revealed by the hole board test [1]. In mouse hippocampal slices, sunifiram at 10-100 nM significantly enhanced LTP in a bell-shaped dose-response relationship which peaked at 10 nM. The enhancement of LTP by sunifiram treatment was inhibited by 7-chloro-kynurenic acid (7-ClKN), an antagonist for glycine-binding site of NMDAR, but not by ifenprodil, an inhibitor for polyamine site of NMDAR [2].in vivo: OBX mice were administered once a day for 7-12 days with sunifiram (0.01-1.0 mg/kg p.o.) from 10 days after operation with or without gavestinel (10 mg/kg i.p.), which is glycine-binding site inhibitor of N-methyl-d-aspartate receptor (NMDAR) [3].

  • CAS Number: 314728-85-3
  • MF: C14H18N2O2
  • MW: 246.305
  • Catalog: iGluR
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 442.0±38.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 205.0±19.1 °C

N'-propan-2-ylpyridine-4-carbohydrazide

Iproniazid is a non-selective, irreversible monoamine oxidase (MAO) inhibitor of the hydrazine class. Iproniazid has antidepressive activity[1].

  • CAS Number: 54-92-2
  • MF: C9H13N3O
  • MW: 179.21900
  • Catalog: Monoamine Oxidase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Catharanthine

Catharanthine inhibits nicotinic receptor mediated diaphragm contractions with IC50 of 59.6 μM.Target: nAChRCatharanthine evokes a concentration-dependent attenuation of carbachol responses in the rat ileum preparation, producing rightward curve displacements and decreases in maximal agonist responses. The mixture of serpentine, plus ajmalicine and catharanthine reveals a concentration-dependent inhibitory effect of acethylcholinesterase (AchE), with an IC50 at ca. 2.25 μg/Ml [1]. Catharanthine can induce the self-association of tubulin into linear indefinite polymers with an efficacy that is 75% that of vinblastine or vincristine. Catharanthine binds to tubulin alpha-beta dimer with binding constant of 2.8 mM [2]. Catharanthine stimulates release of amylase from pancreatic fragments and to cause extensive degranulation of pancreatic acinar cells with accumulation of membrane material in the Golgi region. Catharanthine induces a delayed release of Ca2+ from prelabeled pancreatic fragments as compared to bethanechol [3]. Catharanthine inhibits epibatidine-induced Ca(2+) influx in TE671-α, -β, -γ, -δ cells in a noncompetitive manner with similar potencies IC50 of 17 mM-25 mM. Catharanthine inhibits [3H]TCP binding to the desensitized Torpedo AChR with higher affinity compared to the resting AChR. Catharanthine enhances [3H]cytisine binding to resting but activatable Torpedo AChRs, suggesting desensitizing properties [4].

  • CAS Number: 2468-21-5
  • MF: C21H24N2O2
  • MW: 336.427
  • Catalog: nAChR
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 491.5±45.0 °C at 760 mmHg
  • Melting Point: 138-140ºC
  • Flash Point: 251.1±28.7 °C

Topiramate D12

Topiramate D12 (McN 4853 D12) is a deuterium labeled Topiramate. Topiramate is a broad-spectrum antiepileptic agent. Topiramate is a GluR5 receptor antagonist. Topiramate produces its antiepileptic effects through enhancement of GABAergic activity, inhibition of kainate/AMPA receptors, inhibition of voltage-sensitive sodium and calcium channels, increases in potassium conductance, and inhibition of carbonic anhydrase[1][2][3].

  • CAS Number: 1279037-95-4
  • MF: C12H9D12NO8S
  • MW: 351.436
  • Catalog: Calcium Channel
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 438.7±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 219.1±31.5 °C

Venlafaxine-d6-1

Venlafaxine-d6-1 is deuterium labeled Venlafaxine. Venlafaxine (Wy 45030) is an orally active, potent serotonin (5-HT)/norepinephrine (NE) reuptake dual inhibitor. Venlafaxine is an antidepressant[1].

  • CAS Number: 940297-06-3
  • MF: C17H21D6NO2
  • MW: 283.44
  • Catalog: Serotonin Transporter
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MR2938

MR2938 is a potent AChE inhibitor, with an IC50 of 5.04 μM. MR2938 also suppresses NO production obviously (IC50 = 3.29 μM). MR2938 suppresses the neuroinflammation through blocking MAPK/JNK and NF-κB signaling pathways. MR2938 can be used for Alzheimer’s disease (AD) research[1].

  • CAS Number: 1044870-65-6
  • MF: C21H24N4O3
  • MW: 380.44
  • Catalog: CCR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

N-Desethyloxybutynin hydrochloride

N-Desethyloxybutynin hydrochloride is an active metabolite of Oxybutynin. N-Desethyloxybutynin hydrochloride binds to mAChRs in isolated? human bladder and human parotid gland with pKi values of 8.2 and 8.7, respectively[1].

  • CAS Number: 81039-77-2
  • MF: C20H28ClNO3
  • MW: 365.89400
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 136-138ºC
  • Flash Point: N/A

FFN246

Novel fluorescent substrate for both the serotonin transporter and the vesicular monoamine transporter 2 (VMAT2)

  • CAS Number: 2210244-83-8
  • MF: C15H14ClFN2O
  • MW: 292.74
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NGB 2904 hydrochloride

NGB 2904 hydrochloride is a potent, selective, orally active and brain-penetrated antagonist of dopamine D3 receptor, with a Ki of 1.4 nM. NGB 2904 hydrochloride shows selectivity for D3 over D2, 5-HT2, α1, D4, D1 and D5 receptors (Kis=217, 223, 642, >5000, >10000 and >10000 nM, respectively). NGB 2904 hydrochloride antagonizes Quinpirole-stimulated mitogenesis. NGB 2904 hydrochloride can inhibit Cocaine's rewarding effects and Cocaine-induced reinstatement of drug-seeking behavior[1][2].

  • CAS Number: 189061-11-8
  • MF: C28H30Cl3N3O
  • MW: 530.916
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(rel)-Asperparaline A

(rel)-Asperparaline A ((rel)-Aspergillimide), an anthelmintic metabolite, is isolated from okara that has been fermented with Aspergillus japonicas JV-23. (rel)-Asperparaline A is also a potent and selective antagonist of nAChR. (rel)-Asperparaline A exhibits paralytic activity in silk worms[1][2].

  • CAS Number: 195966-93-9
  • MF: C20H29N3O3
  • MW: 359.463
  • Catalog: nAChR
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 546.1±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 244.6±22.5 °C

PCS1055 dihydrochloride

PCS1055 dihydrochloride is a potent, selective and competitive muscarinic M4 receptor antagonist with an IC50 of 18.1 nM and a Kd of 5.72 nM. PCS1055 dihydrochloride inhibits radioligand [3H]-NMS binding to the M4 receptor with a Ki of 6.5 nM. PCS1055 dihydrochloride exhibits >100-fold selectivity over M1-, M3-, and M5-receptors and 30-fold selectivity at the M2 receptor. PCS1055 dihydrochloride is also a potent AChE inhibitor with IC50 s of 22 nM and 120 nM for electric eel and human AChE, respectively[1][2].

  • CAS Number: 361979-40-0
  • MF: C27H34Cl2N4
  • MW: 485.49
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

5-HT2C agonist-3 free base

5-HT2C agonist-3 ((+)-19) free base is a selective 5-HT2C agonist (EC50: 24 nM, Ki: 78 nM). 5-HT2C agonist-3 free base has antipsychotic drug-like activity. 5-HT2C agonist-3 free base blocks Amphetamine-induced hyperactivity[1].

  • CAS Number: 2104810-17-3
  • MF: C19H22FNO2
  • MW: 315.38
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ibodutant

MEN 15596 is a potent and selective tachykinin NK2 receptor antagonist with a pKi of 10.1.

  • CAS Number: 522664-63-7
  • MF: C37H48N4O4S
  • MW: 644.86600
  • Catalog: Neurokinin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Arbaclofen placarbil

Arbaclofen placarbil is a novel transported prodrug of the active R-isomer of baclofen. Baclofen is a racemic GABAB receptor agonist

  • CAS Number: 847353-30-4
  • MF: C19H26ClNO6
  • MW: 399.866
  • Catalog: GABA Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 545.1±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 283.5±30.1 °C

Prucalopride-13C,d3

Prucalopride-13C,d3 is the 13C- and deuterium labeled.

  • CAS Number: 2140306-00-7
  • MF: C1713CH23D3ClN3O3
  • MW: 371.88
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(+)-Norfenfluramine hydrochloride

(+)-Norfenfluramine hydrochloride, a major hepatic metabolite of (+)-fenfluramine, is a selective 5-HT2B receptor agonist (Ki: 11.2 nM). (+)-Norfenfluramine hydrochloride potently stimulates the hydrolysis of inositol phosphates and increases intracellular Ca2+. (+)-Norfenfluramine hydrochloride can be used for the research of primary pulmonary hypertension and valvular heart disease[1].

  • CAS Number: 37936-89-3
  • MF: C10H13ClF3N
  • MW: 239.66500
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MAO-IN-3

MAO-IN-3 (Compound 5) is a reversible and competitive MAO inhibitor (Ki: 0.6 and 0.2 μM for MAO A and MAO B). MAO-IN-3 inhibits LN-229 glioblastoma cell proliferation with an IC50 of 0.8 μM. MAO-IN-3 can be used for cancer research[1].

  • CAS Number: 797805-26-6
  • MF: C42H54N4O4
  • MW: 678.90
  • Catalog: Monoamine Oxidase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

beta-lipotropin (60-65)

β-Lipotropin (60-65) (β-LPH (60-65)), an opioid peptide, is a potent opioid agonist[1].

  • CAS Number: 60117-19-3
  • MF: C33H47N9O8S
  • MW: 729.84700
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

α-Conotoxin MrIC

α-Conotoxin MrIC is an α7nAChR biased agonist. α-Conotoxin MrIC exclusively activates α7nAChR regulated by type II positive allosteric modulators, including PNU120596. α-Conotoxin MrIC can be used to study neurological diseases and also to probe the pharmacological properties of α7nAChR[1].

  • CAS Number: 1417816-41-1
  • MF: C74H111N23O24S4
  • MW: 1835.07
  • Catalog: nAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AChE/BChE-IN-2

AChE/BChE-IN-2 (Compound 13b) is a potent inhibitor of AChE/BChE (AChE IC50 = 0.96 ± 0.14 µM, BChE IC50 = 1.23 ± 0.23 µM). AChE/BChE-IN-2 has the potential for the research of AD diseases[1].

  • CAS Number: 2761991-42-6
  • MF: C23H25N3O5
  • MW: 423.46
  • Catalog: AChE
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SR 57227 hydrochloride

SR 57227A is a potent, orally active and selective 5-HT3 receptor agonist, with ability to cross the blood brain barrier. SR 57227A has affinities (IC50) varying between 2.8 and 250 nM for 5-HT3 receptor binding sites in rat cortical membranes and on whole NG 108-15 cells or their membranes. Anti-depressant effects[1][2].

  • CAS Number: 77145-61-0
  • MF: C10H15Cl2N3
  • MW: 248.15200
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: 367.6ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 176.1ºC

Amitriptylinoxide

Amitriptylinoxide (Equilibrin) is an analogue and metabolite of amitriptyline with similar antidepressant efficacy[1].

  • CAS Number: 4317-14-0
  • MF: C20H23NO
  • MW: 293.40
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Pipequaline hydrochloride

Pipequaline hydrochloride (PK-8165 hydrochloride) is a partial benzodiazepine receptor agonist with anxiolytic activity[1][2].

  • CAS Number: 80221-58-5
  • MF: C22H25ClN2
  • MW: 352.90
  • Catalog: GABA Receptor
  • Density: N/A
  • Boiling Point: 489.2ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 249.7ºC

Buspirone hydrochloride

Buspirone hydrochloride is an anxiolytic psychotropic drug, is used to treat generalized anxiety disorder (GAD).

  • CAS Number: 33386-08-2
  • MF: C21H32ClN5O2
  • MW: 421.96400
  • Catalog: 5-HT Receptor
  • Density: 1.24g/cm3
  • Boiling Point: 613.9ºC at 760mmHg
  • Melting Point: 201.5-202.50C
  • Flash Point: 325.1ºC

Zolmitriptan-d6

Zolmitriptan-d6 is deuterium labeled Zolmitriptan. Zolmitriptan (BW-311C90; 311C90) is a 5-HT1B/1D receptor partial agonist with Kis of 5.01 nM, 0.63 nM, and 63.09 nM for 5-HT1B, 5-HT1D, 5-HT1F receptor, respectively. Zolmitriptan can be used for the research of migraine[1][2].

  • CAS Number: 1217644-84-2
  • MF: C16H15D6N3O2
  • MW: 293.39
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Lintopride

Lintopride is a 5HT4 antagonist with moderate 5HT3 antagonist properties.

  • CAS Number: 107429-63-0
  • MF: C14H19ClN4O2
  • MW: 310.77900
  • Catalog: 5-HT Receptor
  • Density: 1.35g/cm3
  • Boiling Point: 494.1ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 252.6ºC

Sarpogrelate Hydrochloride

Sarpogrelate(MCI-9042) hydrochloride, a selective 5-HT2 antagonist, has been widely used as an anti-platelet agent for the treatment of PAD.Target: 5-HT2 RecepterSarpogrelate is a drug which acts as an antagonist at the 5HT2A and 5-HT2B receptors. Sarpogrelate was shown to have the same affinity as ritanserin for 5-HT2A receptors, with a Ki value of 8.39 nM [1]. Sarpogrelate lacked prominent 5-HT1-like, 5-HT3, beta, H1, H2 and M3 antagonist activity and weakly blocked alpha 1-adrenoceptors (pKB = 6.30). (S)-M-1 showed weak affinity for 5-HT1-like receptors (pKB = 6.30), alpha 1- (pKB = 6.80) and beta- (pKB = 6.54) adrenoceptors, while (R)-M-1 was a weak antagonist at histamine H1 receptors (pKB = 6.49) [2]. After 12 weeks of sarpogrelate administration, FBF and LBF responses during RH showed significant increases from 13.2 +/- 1.7 to 18.1 +/- 2.2 mL/min per 100 mL tissue (P < 0.01) and from 8.2 +/- 0.9 to 14.2 +/- 2.1 mL/min per 100 mL tissue (P < 0.05), respectively. Sarpogrelate-induced augmentation of FBF and LBF responses to RH was maintained at 24 weeks. Long-term oral administration of sarpogrelate improves vascular function in patients with PAD [3].

  • CAS Number: 135159-51-2
  • MF: C24H32ClNO6
  • MW: 465.967
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: 585.9ºC at 760 mmHg
  • Melting Point: 145-148°C
  • Flash Point: 308.1ºC

Methyl ganoderate A acetonide

Methyl ganoderate A acetonide, a lanostane triterpene, is a natural product that could be isolated from the fruiting bodies of Ganoderma lucidum. Methyl ganoderate A acetonide is a potent AChE inhibitor with an IC50 value of 18.35 μM. Methyl ganoderate A acetonide can be used in research of Alzheimer’s disease (AD)[1].

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

Harmaline

Harmaline is a potent and reversible monoamine oxidase inhibitor in vivo. Harmaline is a central nervous system stimulant and can be used to induce tremor in rodents.

  • CAS Number: 304-21-2
  • MF: C13H14N2O
  • MW: 214.263
  • Catalog: Monoamine Oxidase
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 426.4±45.0 °C at 760 mmHg
  • Melting Point: 232-234 °C(lit.)
  • Flash Point: 211.7±28.7 °C