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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5-AMAM-2-CP

5-AMAM-2-CP is a major metabolite of Acetamiprid. Acetamiprid is a neonicotinoid insecticide used worldwide and is a nAChR agonist[1][2].

  • CAS Number: 864628-19-3
  • MF: C9H11ClN2O
  • MW: 198.65
  • Catalog: nAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Oxatomide

Oxatomide is a potent and orally active dual H1-histamine receptor and P2X7 receptor antagonist with antihistamine and anti-allergic activity. Oxatomide almost completely blocks the ATP-induced current in human P2X7 receptors (IC50 of 0.95 μM). Oxatomide inhibits ATP-induced Ca2+ influx with an IC50 value of 0.43 μM and also inhibits serotonin[1][2].

  • CAS Number: 60607-34-3
  • MF: C27H30N4O
  • MW: 426.55300
  • Catalog: 5-HT Receptor
  • Density: 1.175 g/cm3
  • Boiling Point: 621.1ºC at 760 mmHg
  • Melting Point: 153.60C
  • Flash Point: 329.4ºC

Adrenomedullin (22-52) (human)

Adrenomedullin (AM) (22-52), human is an adrenomedullin receptor antagonist, and also antagonizes the calcitonin generelated peptide (CGRP) receptor in the hindlimb vascular bed of the cat.

  • CAS Number: 159899-65-7
  • MF: C159H252N46O48
  • MW: 3576.03
  • Catalog: Peptides
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ICI 204,448 hydrochloride

ICI-204448 is a κ-opioid agonist with limited access to the CNS, ICI-204448 can displace the binding of the kappa-opioid ligand 3H-bremazocine from guinea pig cerebellum membranes[1].

  • CAS Number: 121264-04-8
  • MF: C23H27Cl3N2O4
  • MW: 501.83
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: 638.9ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 340.2ºC

TMPH hydrochloride

nAChR-IN-1 (hydrochloride) is a tetramethylpiperidine heptanoate, a selective nicotinic acetylcholine receptor (nAChR) inhibitor that inhibits nAChRs lacking α5, α6, or β3 subunits. nAChR-IN-1 has the effect of preventing nerve disorder, can be used for nicotinic acetylcholine receptor dysfunction or neurological disorders research[1].

  • CAS Number: 849461-91-2
  • MF: C16H32ClNO2
  • MW: 305.88
  • Catalog: nAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

N-Methylcalycinine

N-Methylcalycinine is a nature product with AChE inhibitory activity. N-Methylcalycinine can be isolated from the roots of Stephania epigaea. N-Methylcalycinine can be used for the research of asthma, cancer, dysentery, fever, hyperglycemia, intestinal complaints, inflammation, sleep disturbances, tuberculosis and so on[1].

  • CAS Number: 86537-66-8
  • MF: C19H19NO4
  • MW: 325.36
  • Catalog: AChE
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 531.9±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 275.5±30.1 °C

FLB 131

Eticlopride hydrochloride, a selective dopamine D2‐like receptor antagonist, exhibits high affinity for dopamine D2, α1‐adrenergic, α2‐adrenergic, 5HT1, 5HT2 receptors with Kis of 0.09, 112, 699, 6220, and 830 nM, respectively. Antipsychotic agent[1].

  • CAS Number: 97612-24-3
  • MF: C17H26Cl2N2O3
  • MW: 377.306
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 144 - 146 °C
  • Flash Point: N/A

Urapidil-d4 hydrochloride

Urapidil-d4 hydrochloride is the deuterium labeled Urapidil hydrochloride. Urapidil hydrochloride is an α1-adrenoceptor antagonist and 5-HT1A receptor agonist[1][2].

  • CAS Number: 1794979-63-7
  • MF: C20H26D4ClN5O3
  • MW: 427.96
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Doxepin hydrochloride

Doxepin HCl is a tricyclic antidepressant that is marketed worldwide.Target: SSRIsDoxepin inhibits the reuptake of serotonin and norepinephrine and acts as a antagonist at various serotonergic, adrenergic, musacrinic, dopaminergic and histaminergic receptors [1]. In the doxepin-treated patients who completed the study (N = 20, 47.6+/-11.3), medication significantly increased sleep efficiency after acute (night 1, p < or = .001) and subchronic (night 28, p < or = .05) intake compared with the patients who received placebo (N = 20, 47.4+/-16.8 years of age). Doxepin to cause significantly (p < or = .05) better global improvement at the first day of treatment [2].

  • CAS Number: 1229-29-4
  • MF: C19H22ClNO
  • MW: 315.837
  • Catalog: Serotonin Transporter
  • Density: N/A
  • Boiling Point: 413.3ºC at 760mmHg
  • Melting Point: 187-189°C
  • Flash Point: 121.3ºC

Hydroxyamine hydrochloride

Hydroxyamine hydrochloride is a selective monoamine oxidase (MAO) inhibitor used for inhibiting of platelet aggregation. Hydroxyamine hydrochloride is an intermediate of organic synthesis[1].

  • CAS Number: 5470-11-1
  • MF: ClH4NO
  • MW: 69.491
  • Catalog: Monoamine Oxidase
  • Density: 1.67 g/mL at 25 °C(lit.)
  • Boiling Point: 56.5ºC at 760mmHg
  • Melting Point: 155-157 °C (dec.)(lit.)
  • Flash Point: N/A

NoMifensine

Nomifensine maleate is a selective inhibitor of dopamine uptake, used in adult attention deficit disorder.

  • CAS Number: 32795-47-4
  • MF: C20H22N2O4
  • MW: 354.40000
  • Catalog: Dopamine Receptor
  • Density: 1.114g/cm3
  • Boiling Point: 378.4ºC at 760mmHg
  • Melting Point: 179-181ºC
  • Flash Point: 164ºC

Ziprasidone HCl

Ziprasidone Hcl(CP-88059 Hcl) is a combined 5-HT (serotonin) and dopamine receptor antagonist which exhibits potent effects of antipsychotic activity.Target: 5-HT receptor; Dopamine receptorZiprasidone (hydrochloride) is the salt form of ziprasidone, which possesses an in vitro 5-HT2A/dopamine D2 receptor affinity ratio higher than any clinically available antipsychotic agent. In vivo, ziprasidone antagonizes 5-HT2A receptor-induced head twitch with 6-fold higher potency than for blockade of d-amphetamine-induced hyperactivity, a measure of central dopamine D2 receptor antagonism. Ziprasidone also has high affinity for the 5-HT1A, 5-HT1D and 5-HT2C receptor subtypes, which may further enhance its therapeutic potential [1]. Ziprasidone sulfoxide and sulfone were the major metabolites in human serum. The affinities of the sulfoxide and sulfone metabolites for 5-HT2 and D2 receptors are low with respect to ziprasidone, and are thus unlikely to contribute to its antipsychotic effects [2]. Ziprasidone was associated with significant differential adverse effects relative to placebo in BPM, BPD, and schizophrenia with no significant difference in weight gain in all 3 groups. Self-reported somnolence was increased across the 3 conditions. Subjects with BPM were more vulnerable to EPS than those with BPD or schizophrenia [3].Clinical indications: Bipolar I disorder; Bipolar disorder; Mania; SchizophreniaFDA Approved Date: February 2001

  • CAS Number: 122883-93-6
  • MF: C21H22Cl2N4OS
  • MW: 449.397
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

N20C hydrochloride

N20C hydrochloride is a selective and noncompetitive open NMDA receptor open channel blocker, with micromolar affinity, fast on-off blockade kinetics, and strong voltage dependence. Neuroprotective activity[1].

  • CAS Number: 1177583-87-7
  • MF: C17H21ClN2O
  • MW: 304.81
  • Catalog: iGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NMDAR/TRPM4 inhibitor 8

NMDAR/TRPM4-IN-2 free base (compound 8) is a potent NMDAR/TRPM4 interaction interface inhibitor. NMDAR/TRPM4-IN-2 free base shows neuroprotective activity. NMDAR/TRPM4-IN-2 free base prevents NMDA-induced cell death and mitochondrial dysfunction in hippocampal neurons, with an IC50 of 2.1 μM. NMDAR/TRPM4-IN-2 free base protects mice from MCAO-induced brain damage and NMDA-induced retinal ganglion cell loss[1].

  • CAS Number: 1353979-43-7
  • MF: C11H17BrN2
  • MW: 257.17
  • Catalog: ERK
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 300.6±22.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 135.6±22.3 °C

(Rac)-WAY-161503

(Rac)-WAY-161503 is a potent, selective, highly affinity 5-HT2C receptor agonist with a Ki of 4 nM and an EC50 of 12 nM. (Rac)-WAY-161503 displays higher affinity for 5-HT2C than 5-HT2A and 5-HT2B receptors. (Rac)-WAY-161503 has anti-obesity and antidepressant effects[1][2].

  • CAS Number: 75704-24-4
  • MF: C11H11Cl2N3O
  • MW: 308.59100
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: 529ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 273.7ºC

Neostigmine Methylsulfate

Neostigmine methyl sulfate is a reversible inhibitor of acetylcholinesterase, can not cross the blood-brain barrier.

  • CAS Number: 51-60-5
  • MF: C13H22N2O6S
  • MW: 334.389
  • Catalog: AChE
  • Density: N/A
  • Boiling Point: 457ºC
  • Melting Point: 175-177 °C(lit.)
  • Flash Point: N/A

Azaphen

Pipofezine(Azafen or Azaphen) is a potent inhibitor of the reuptake of serotonin. IC50 Value: Target: SSRIsPipofezine is a tricyclic antidepressant (TCA) approved in Russia for the treatment of depression. In addition to its antidepressant action, pipofezine has sedative effects as well, indicating antihistamine activity.

  • CAS Number: 24853-80-3
  • MF: C16H21Cl2N5O
  • MW: 370.27700
  • Catalog: Serotonin Transporter
  • Density: N/A
  • Boiling Point: 536ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 278ºC

5HT6-ligand-1

5HT6-ligand-1 is a potent 5-HT6 receptor ligand with a Ki of 1.43 nM.

  • CAS Number: 1038988-11-2
  • MF: C20H22BrN3O2S
  • MW: 448.38
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Molindone

Molindone ((±)-Molindone), an indole derivative, is a potent dopamine D2 and D5 receptor antagonist. Molindone ((±)-Molindone) can be used for the research of schizophrenia and severe mental illness[1][2].

  • CAS Number: 7416-34-4
  • MF: C16H24N2O2
  • MW: 276.37400
  • Catalog: Dopamine Receptor
  • Density: 1.14 g/cm3
  • Boiling Point: 462.9ºC at 760 mmHg
  • Melting Point: 180 - 181ºC
  • Flash Point: 233.7ºC

Nuvenzepine

Nuvenzepine is an mAChR antagonist previously in phase I clinical trials for the treatment of gastrospasm.

  • CAS Number: 96487-37-5
  • MF: C19H20N4O2
  • MW: 336.38800
  • Catalog: mAChR
  • Density: 1.267g/cm3
  • Boiling Point: 522.3ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 269.7ºC

M1/M2/M4 muscarinic agonist 3

M1/M2/M4 muscarinic agonist 3 (compound 45) is a muscarinic mAChR M1/M2/M4 agonist with EC50s of 3.2 nM, 32 nM and 1.7 nM, respectively[1].

  • CAS Number: 2640109-28-8
  • MF: C23H31FN2O3
  • MW: 402.50
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bupropion D9

Bupropion D9 is a deuterium labeled Bupropion. Bupropion is an atypical antidepressant of the aminoketone group and inhibits dopamine, norepinephrine reuptake and blocks several nicotinic receptors[1].

  • CAS Number: 150988-80-0
  • MF: C13H9D9ClNO
  • MW: 248.79700
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

OM99-2 trifluoroacetate salt

OM99-2, an eight residue peptidomimetic, tight-binding inhibitor of human brain memapsin 2 with a Ki value of 9.58 nM[1]. OM99-2 is significantly advanced the development of BACE1 inhibitor[2], has the potential for the research of the Alzheimer's disease[3].

  • CAS Number: 314266-76-7
  • MF: C41H64N8O14
  • MW: 892.99200
  • Catalog: Beta-secretase
  • Density: 1.311g/cm3
  • Boiling Point: 1322.4ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 753.6ºC

FG-5893

FG-5893 is a 5-HT1A receptor agonist and a 5-HT2 receptor antagonist. FG-5893 has anxiolytic effect[1][2].

  • CAS Number: 150527-23-4
  • MF: C27H29F2N3O2
  • MW: 465.53500
  • Catalog: 5-HT Receptor
  • Density: 1.201g/cm3
  • Boiling Point: 598.6ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 315.8ºC

Carburazepam

Carburazepam is a drug which derives from benzodiazepine. Benzodiazepines (BZD, BZs) are a class of psychoactive drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring.

  • CAS Number: 59009-93-7
  • MF: C17H16ClN3O2
  • MW: 329.78100
  • Catalog: GABA Receptor
  • Density: 1.334g/cm3
  • Boiling Point: 565.5ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 295.8ºC

E 2012

E 2012 is a potent γ-secretase modulator.IC50 value:Target: γ-secretaseIn the present study, 9 dogs were treated with a single dose of the γ-secretase modulator E2012, the γ-secretase inhibitor LY450139, or vehicle with a dosing interval of 1 week. The isoform Aβ(1-37) was significantly increased in a dose-dependent manner in response to treatment with E2012, while Aβ(1-39), Aβ(1-40) and A(1-42) decreased [1].E2012, a gamma secretase modulator without affecting Notch processing, aimed at Alzheimer's disease by reduction of amyloid β-42, induced cataract following repeated doses in the rat.E2012 inhibits 3β-hydroxysterol Δ24-reductase (DHCR24) at the final step in the cholesterol biosynthesis. In vivo lenticular concentration of E2012 after 13-week repeated dose with cataract was well above those where inhibition was observed in vitro.E2012 induces cataract in the rat by inhibiting DHCR24 at the final step of cholesterol synthesis with associated elevation in desmosterol within the lens, preceded by desmosterol changes that would serve as a predictive safety biomarker for lenticular opacity [2].

  • CAS Number: 870843-42-8
  • MF: C25H26FN3O2
  • MW: 419.49100
  • Catalog: γ-secretase
  • Density: 1.195g/cm3
  • Boiling Point: 649.168ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 346.405ºC

N-Desmethylclozapine-d8 hydrochloride

Desmethylclozapine-d8 (Norclozapine-d8) hydrochloride is the deuterium labeled N-Desmethylclozapine hydrochloride. N-Desmethylclozapine hydrochloride is a major active metabolite of the atypical antipsychotic drug Clozapine. N-Desmethylclozapine hydrochloride is a potent, allosteric and partial M1 receptors agonist (EC50=115 nM) and is able to potentiate hippocampal N-methyl-d-aspartate (NMDA) receptor currents through M1 receptor activation. N-Desmethylclozapine hydrochloride is also a δ-opioid agonist[1][2][3].

  • CAS Number: 2705402-91-9
  • MF: C17H10D8Cl2N4
  • MW: 357.31
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

5-HT7 receptor ligand 1

5-HT7 receptor ligand 1 (Compound 5c) is a 5-HT7 receptor ligand with a Ki of 8 nM. 5-HT7 receptor ligand 1 is not hepatotoxic and exhibit moderate potential interaction with other drugs metabolized by CYP3A4 or CYP2D6[1].

  • CAS Number: 2758571-64-9
  • MF: C21H23N7
  • MW: 373.45
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

3-aminopropanenitrile,hydrochloride

β-Aminopropionitrile (BAPN) hydrochloride is a specific, irreversible and orally active lysyl oxidase (LOX) inhibitor. β-Aminopropionitrile hydrochloride targets the active site of LOX or LOXL isoenzymes[1][2].

  • CAS Number: 646-03-7
  • MF: C3H7ClN2
  • MW: 106.55400
  • Catalog: Monoamine Oxidase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Picrotoxinin

Picrotoxinin, a potent convulsant, is a chloride channel blocker. Picrotoxinin is a noncompetitive GABAA receptor antagonist, which negatively modulates the action of GABA on GABAA receptors[1].

  • CAS Number: 17617-45-7
  • MF: C15H16O6
  • MW: 292.28400
  • Catalog: Chloride Channel
  • Density: 1.52g/cm3
  • Boiling Point: 551.6ºC at 760mmHg
  • Melting Point: 203-205ºC
  • Flash Point: 214ºC