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.


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Opioid receptor modulator 1

Opioid receptor modulator 1 is a opioid receptor modulator extracted from patent WO2014072809A2, Compound RA11 in EXAMPLE 7.

  • CAS Number: 77514-44-4
  • MF: C18H23NO2
  • MW: 285.38
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Citalopram hydrobromide

Citalopram hydrobromide is an antidepressant drug of the selective serotonin reuptake inhibitor (SSRI) class. It has US FDA approval to treat major depression.

  • CAS Number: 59729-32-7
  • MF: C20H22BrFN2O
  • MW: 405.304
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: 182-188ºC
  • Melting Point: 182-188ºC
  • Flash Point: 212.8ºC

Felbamate-d5

Felbamate-d5 is the deuterium labeled Felbamate[1]. Felbamate (W-554) is a potent nonsedative anticonvulsant whose clinical effect may be related to the inhibition of N-methyl-D-aspartate (NMDA)[2][3].

  • CAS Number: 1191888-51-3
  • MF: C11H9D5N2O4
  • MW: 243.27100
  • Catalog: iGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Fluphenazine decanoate

Fluphenazine decanoate is a long-acting phenothiazine neuroleptic that used to treat schizophrenia. Fluphenazine decanoate is also a high and continuous dopamine D2 receptor blocker[1][2][3].

  • CAS Number: 5002-47-1
  • MF: C32H44F3N3O2S
  • MW: 591.77100
  • Catalog: Dopamine Receptor
  • Density: 1.149 g/cm3
  • Boiling Point: 658.1ºCat 760 mmHg
  • Melting Point: 30-32°
  • Flash Point: 351.8ºC

Picrotoxin

Picrotoxin is a noncompetitive antagonist of GABAA receptor.

  • CAS Number: 124-87-8
  • MF: C15H18O7.C15H16O6
  • MW: 301.29
  • Catalog: GABA Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 203 ℃(lit.)
  • Flash Point: N/A

Chlorpromazine hydrochloride

Chlorpromazine Hydrochloride is an antagonist of the dopamine D2, 5HT2A, potassium channel andsodium channel. Chlorpromazine binds with D2 and 5HT2A with Kis of 363 nM and 8.3 nM, respectively.

  • CAS Number: 69-09-0
  • MF: C17H20Cl2N2S
  • MW: 355.325
  • Catalog: Autophagy
  • Density: 1.077 g/cm3 (15 C)
  • Boiling Point: 450.1ºC at 760 mmHg
  • Melting Point: 192-196°C
  • Flash Point: N/A

YQA14

YQA14 is a selective antagonist of D3 receptor.

  • CAS Number: 1221408-42-9
  • MF: C23H27ClN4O3
  • MW: 442.94
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(+)-Norfenfluramine

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

  • CAS Number: 19036-73-8
  • MF: C10H12F3N
  • MW: 203.20400
  • Catalog: 5-HT Receptor
  • Density: 1.152g/cm3
  • Boiling Point: 215.2ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 88.9ºC

JNJ-67569762

JNJ-67569762 is a selective BACE1 inhibitor targeting the S3 pocket (IC50 = 2.7 nM).

  • CAS Number: 2380313-26-6
  • MF: C22H22F4N4O5S
  • MW: 530.49
  • Catalog: Beta-secretase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(Rac)-Rotigotine hydrochloride

rac-Rotigotine Hcl is a high potency and selectivity agonist for D-2 receptor with Ki of 0.69 nM. IC50 Value: 0.69 nM(Ki)Target: D-2 receptorin vitro: rac-Rotigotine showed high potency (Ki = 0.69 nM) and selectivity for D-2 receptors as compared to its potency and selectivity at various other neuronal receptors (Ki in nM): D-1 (678) dopamine, alpha 1-(534) and alpha 2-(195) adrenoceptor, S1-(6940) and S2-(5900) serotonin and muscarine (2660). Very low activity (Ki greater than 10(-5) M) was seen at the beta-adrenoceptor, A1-adenosine, GABAA and benzodiazepine receptors. Furthermore, rac-Rotigotine inhibited the calcium-dependent release of [3H]dopamine (IC50: 4 nM) and [3H]acetylcholine (IC50: 6.3 nM) from rabbit striatal slices in the nanomolar range. These effects of rac-Rotigotine were mediated through activation of D-2 dopamine autoreceptors and D-2 dopamine heteroreceptors, respectively.in vivo: Presynaptic dopaminergic activity in vivo was measurable as an inhibition of the locomotor activity of mice, and in this model rac-Rotigotine was more effective than apomorphine. Moreover, the effect of rac-Rotigotine could be antagonized by sulpiride but not by yohimbine. rac-Rotigotine was equipotent with apomorphine in inducing circling behaviour in 6-OHDA-lesioned rats. rac-Rotigotine had almost no serotonergic activity in vivo.

  • CAS Number: 102120-99-0
  • MF: C19H26ClNOS
  • MW: 351.93400
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

COX-2-IN-22

COX-2-IN-22 (Compound 4h) is a COX-2 inhibitor with an IC50 of 8.6 µM. COX-2-IN-22 also inhibits AChE, BChE, β-Secretase, LOX-5 and DPPH with IC50 values of 2.8, 6.3, 15.3, 13.9 and 6.8 µM, respectively. COX-2-IN-22 can cross BBB[1].

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

L-685,458

L-685458 is a potent inhibitor of Amyloid β-Protein precursor γ-secretase activity with IC50 of 17 nM, shows greater than 50-100-fold selectivity over other aspartyl proteases tested.IC50 value: 17 nMTarget: γ-secretasein vitro: L-685458 is a Notch inhibitor. L-685458 blocks Notch activation in the two cell lines in terms of reduced cytoplasmic distribution and almost diminished nuclear labelling of Hes1 proteins. [2] L-685458 is a γ-secretase inhibitor. [3]

  • CAS Number: 292632-98-5
  • MF: C39H52N4O6
  • MW: 672.85300
  • Catalog: γ-secretase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Coumaran

Coumaran (2,3-Dihydrobenzofuran) is an acetylcholinesterase (AChE) inhibitor isolated from leaves of L. camara. Coumaran can be used as a biopesticide[1].

  • CAS Number: 496-16-2
  • MF: C8H8O
  • MW: 120.148
  • Catalog: AChE
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 188.2±10.0 °C at 760 mmHg
  • Melting Point: -21°C
  • Flash Point: 66.7±0.0 °C

NGD 94-1

NGD94-1 is a specific dopamine D4 receptor antagonist. NGD94-1 can effectively reverse Phencyclidine-induced cognitive impairment in marmosets. NGD94-1 can be used in the study of psychiatric diseases[1].

  • CAS Number: 178928-68-2
  • MF: C18H20N6
  • MW: 320.39
  • Catalog: Dopamine Receptor
  • Density: 1.259g/cm3
  • Boiling Point: 578.2ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 303.5ºC

Methyl tridecanoate

Methyl tridecanoate moderately inhibits β-amyloid aggregation. Methyl tridecanoate weakly inhibits acetylcholinesterase (AChE)[1].

  • CAS Number: 1731-88-0
  • MF: C14H28O2
  • MW: 228.371
  • Catalog: AChE
  • Density: 0.9±0.1 g/cm3
  • Boiling Point: 289.6±0.0 °C at 760 mmHg
  • Melting Point: 5.5 °C(lit.)
  • Flash Point: 124.9±6.9 °C

Olcegepant hydrochloride

Olcegepant hydrochloride is the first potent and selective non-peptide antagonist of the calcitonin gene-related peptide 1 (CGRP1) receptor with IC50 of 0.03 nM and with a Ki of 14.4 pM for human CGRP.

  • CAS Number: 586368-06-1
  • MF: C38H47Br2N9O5.HCl
  • MW: 906.11
  • Catalog: CGRP Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SB 242084

SB 242084 hydrochloride is a 5-HT2C receptor antagonist(pKi=9.0) that displays 158- and 100-fold selectivity over 5-HT2A and 5-HT2B receptors respectively.IC50 value: 9.0(pKi) [1]Target: 5-HT2C antagonistin vitro: SB 242084 had over 100-fold selectivity over a range of other 5-HT, dopamine and adrenergic receptors. In studies of 5-HT-stimulated phosphatidylinositol hydrolysis using SH-SY5Y cells stably expressing the cloned human 5-HT2C receptor, SB 242084 acted as an antagonist with a pKb of 9.3, which closely resembled its corresponding receptor binding affinity [1].in vivo: SB 242084 potently inhibited m-chlorophenylpiperazine (mCPP, 7 mgkg i.p. 20 min pre-test)-induced hypolocomotion in rats, a model of in vivo central 5-HT2C receptor function, with an ID50 of 0.11 mg/kg i.p., and 2.0 mg/kg p.o. SB 242084 (0.1-1 mg/kg i.p.) exhibited an anxiolytic-like profile in the rat social interaction test, increasing time spent in social interaction, but having no effect on locomotion. SB 242084 (0.1-1 mg/kg i.p.) also markedly increased punished responding in a rat Geller-Seifter conflict test of anxiety, but had no consistent effect on unpunished responding [1].

  • CAS Number: 1049747-87-6
  • MF: C21H21Cl3N4O2
  • MW: 467.78
  • Catalog: 5-HT Receptor
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 620.1±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 328.8±31.5 °C

Nelonicline citrate

Nelonicline (ABT-126) citrate is an orally active and selective α7 nicotinic receptor agonist with high affinity to α7 nAChRs in human brain (Ki=12.3 nM). Nelonicline citrate is used for the research of shizophrenia and Alzheimer's disease[1][2][3].

  • CAS Number: 1026136-84-4
  • MF: C23H27N3O8S
  • MW: 505.54
  • Catalog: nAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(R)-Rivastigmine (D6 tartrate)

(R)-Rivastigmine D6 (tartrate) is the deuterium labeled (R)-Rivastigmine, which is an cholinesterase inhibitor.

  • CAS Number: 194930-00-2
  • MF: C18H22D6N2O8
  • MW: 406.46000
  • Catalog: AChE
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Acamprosate-d3 (calcium salt)

Acamprosate D3 calcium is the deuterium labeled Acamprosate calcium. Acamprosate calcium is a GABA receptor agonist and modulator of glutamatergic systems[1][2].

  • CAS Number: 1225580-94-8
  • MF: C5H7CaD3NO4S
  • MW: 223.29900
  • Catalog: GABA Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Efaroxan hydrochloride

Efaroxan hydrochloride is a potent and selective α2-adrenoceptor antagonist, antidiabetic activity. Efaroxan hydrochloride is a selective I1-Imidazoline receptor antagonist and can be used for the research of cardiovascular disease[1][2][3].

  • CAS Number: 89197-00-2
  • MF: C13H17ClN2O
  • MW: 252.740
  • Catalog: Adrenergic Receptor
  • Density: N/A
  • Boiling Point: 387ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 187.9ºC

MAO A/HSP90-IN-2

MAO A/HSP90-IN-2 (compound 4-C) is a dual inhibitor of HSP90and MAO A with the IC50 values of 0.016 and 4.58 μM, respectively. MAO A/HSP90-IN-2 increases HSP70 expression and reduces HER2 and phospho-Akt expression, and decreases IFN-γ induced PD-L1 expression in GL26 cells. MAO A/HSP90-IN-2 inhibits the growth of Temozolomide (HY-17364) -sensitive and -resistant GBM cells, colon cancer, leukemia, non-small cell lung and other cancers, and has potential to inhibit tumor immune escape[1].

  • CAS Number: 2927489-99-2
  • MF: C25H31ClN2O4
  • MW: 458.98
  • Catalog: HSP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ABT-089

Pozanicline (ABT-089) selectively activate neuronal nicotinic acetylcholine receptor (nAChR) subtypes, is a novel cholinergic agent that is a partial agonist at α4β2* nAChRs (Ki=16 nM) and shows high selectivity for α6β2* and α4α5β2 nAChR subtypes, the binding affinity (Ki, rat) for Pozanicline to [3H] cytisine sites is 16.7 nM.Pozanicline reverses nicotine withdrawal-induced cognitive deficits, may be an effective component of novel therapeutic strategies for nicotine addiction[1].

  • CAS Number: 161417-03-4
  • MF: C11H16N2O
  • MW: 192.25800
  • Catalog: nAChR
  • Density: 1.046g/cm3
  • Boiling Point: 302.7ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 136.9ºC

Substance P acetate salt

Substance P is a neuropeptide, acting as a neurotransmitter and as a neuromodulator.The endogenous receptor for substance P is neurokinin 1 receptor (NK1-receptor, NK1R). Sequence: Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2.

  • CAS Number: 33507-63-0
  • MF: C63H98N18O13S
  • MW: 1347.630
  • Catalog: Peptides
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Talipexole

Talipexole (B-HT920) is a dopamine agonist that has been proposed as an antiparkinsonian agent.Target: Dopamine ReceptorB-HT920 is a selective alpha 2-adrenoceptor agonist. The effects of B-HT920 have been specified using the alpha-adrenergic antagonists yohimbine and prazosin and the dopamine antagonist haloperidol. Yohimbine could not antagonize any of the actions of B-HT920. Pretreatment with prazosin showed a decrease in the loss of body weight caused by B-HT920, while pretreatment with yohimbine showed that B-HT920 induced an increased loss in body weight. These data suggest that B-HT920 under certain conditions exerts dopamine-agonistic actions in stimulating locomotor activity and alpha 1-adrenergic actions in inducing salivation and enhanced loss of body weight [1]. Concomitant treatment with talipexole, an anti-parkinsonian drug, inhibited MPTP-induced autolysis and individual death in a concentration-dependent manner. Pramipexole showed a similar protective effect. In addition, post-treatment with talipexole at 1 hr after MPTP completely inhibited MPTP-induced individual death. Although MPTP treatment caused 30% of the planarians to undergo autolysis and individual death within 12 hr, post-treatment with talipexole even at 12 hr completely rescued the remaining 70% of the planarians from death. These results suggest that the MPTP-treated planarian may be useful as a novel parkinsonian model in which talipexole has a protective effect even in the case of post-treatment [2].

  • CAS Number: 101626-70-4
  • MF: C10H15N3S
  • MW: 209.31
  • Catalog: Dopamine Receptor
  • Density: 1.167g/cm3
  • Boiling Point: 364.6ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 174.3ºC

Zelquistinel

Zelquistinel is a N-methyl-D-aspartate (NMDA) receptor partial agonist used for the research of depression, anxiety and other related psychiatric disorders[1].

  • CAS Number: 2151842-64-5
  • MF: C15H25N3O5
  • MW: 327.38
  • Catalog: iGluR
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 564.0±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 294.9±30.1 °C

Acetamiprid

Acetamiprid is a neonicotinoid insecticide used worldwide. Acetamiprid is a nicotinic acetylcholine receptor (nAChR) agonist, and is shown to be associated with neuromuscular and reproductive disorders[1][2].

  • CAS Number: 135410-20-7
  • MF: C10H11ClN4
  • MW: 222.674
  • Catalog: nAChR
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 352.4±52.0 °C at 760 mmHg
  • Melting Point: 101-103ºC
  • Flash Point: 166.9±30.7 °C

Flibanserin D4

Flibanserin D4 is a deuterium labeled Flibanserin (BIMT-17). Flibanserin is a full agonist of the serotonin 5-HT1A receptor (Ki=1 nM) and an antagonist of 5-HT2A (49 nM)[1].

  • CAS Number: 2122830-90-2
  • MF: C20H17D4F3N4O
  • MW: 394.43
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Glycine-2-13C,15N

Glycine-2-13C,15N is the 13C- and 15N-labeled Glycine. Glycine is an inhibitory neurotransmitter in the CNS and also acts as a co-agonist along with glutamate, facilitating an excitatory potential at the glutaminergic N-methyl-D-aspartic acid (NMDA) receptors.

  • CAS Number: 91795-59-4
  • MF: C13CH515NO2
  • MW: 75.067
  • Catalog: iGluR
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 240.9±23.0 °C at 760 mmHg
  • Melting Point: 240ºC (dec.)(lit.)
  • Flash Point: 99.5±22.6 °C

(S)-AMPA(mM/ml)

(S)-AMPA (L-AMPA), an active S-enantiomer of AMPA, is a potent and selective AMPA receptor agonist[1][2].

  • CAS Number: 83643-88-3
  • MF: C7H10N2O4
  • MW: 186.165
  • Catalog: iGluR
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 425.6±45.0 °C at 760 mmHg
  • Melting Point: 118-122 °C(lit.)
  • Flash Point: 211.2±28.7 °C