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 >
Arenavirus Bacterial CMV Enterovirus Filovirus Fungal HBV HCV HIV HSV Influenza Virus Parasite Reverse Transcriptase RSV SARS-CoV
Antibody-drug Conjugate >
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Apoptosis >
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Antifolate APC ATM/ATR Aurora Kinase Casein Kinase CDK Checkpoint Kinase (Chk) CRISPR/Cas9 Deubiquitinase DNA Alkylator/Crosslinker DNA-PK DNA/RNA Synthesis Eukaryotic Initiation Factor (eIF) G-quadruplex Haspin Kinase HDAC HSP IRE1 Kinesin LIM Kinase (LIMK) Microtubule/Tubulin Mps1 Nucleoside Antimetabolite/Analog p97 PAK PARP PERK Polo-like Kinase (PLK) PPAR RAD51 ROCK Sirtuin SRPK Telomerase TOPK Topoisomerase Wee1
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MAPK/ERK Pathway >
ERK JNK KLF MAP3K MAP4K MAPKAPK2 (MK2) MEK Mixed Lineage Kinase MNK p38 MAPK Raf Ribosomal S6 Kinase (RSK)
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Metabolic Enzyme/Protease >
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
Neuronal Signaling >
5-HT Receptor AChE Adenosine Kinase Amyloid-β Beta-secretase CaMK CGRP Receptor COMT Dopamine Receptor Dopamine Transporter FAAH GABA Receptor GlyT iGluR Imidazoline Receptor mAChR Melatonin Receptor Monoamine Oxidase nAChR Neurokinin Receptor Opioid Receptor Serotonin Transporter γ-secretase
NF-κB >
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Akt AMPK ATM/ATR DNA-PK GSK-3 MELK mTOR PDK-1 PI3K PI4K PIKfyve PTEN
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Protein Tyrosine Kinase/RTK >
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D-Ala-Gly-Phe-Met-NH2

D-Ala-Gly-Phe-Met-NH2, an opioid peptide, is a potent opiate δ-receptor agonist[1].

  • CAS Number: 82948-89-8
  • MF: C19H29N5O4S
  • MW: 423.53
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

S 14506 hydrochloride

S-14506 hydrochloride is a potent 5-HT1A agonist. S-14506 hydrochloride displays dopamine antagonist properties by blocking dopamine D2 receptors. S-14506 hydrochloride inhibits the in vivo binding of [3H]raclopride in striatum and olfactory bulbs. S-14506 hydrochloride has the potential for the research of anxiolytic agent[1][2].

  • CAS Number: 286369-38-8
  • MF: C24H27ClFN3O2
  • MW: 443.941
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(+)-PD 128,907 HCl

(+)-PD 128907 hydrochloride is a selective dopamine D2/D3 receptor agonist, with Kis of 1.7, 0.84 nM for human and rat D3 receptors, 179, 770 n M for human and rat D3 receptors, respectively.

  • CAS Number: 300576-59-4
  • MF: C14H20ClNO3
  • MW: 285.76700
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: 389ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 189ºC

Huperzine A

Huperzine A, an active Lycopodium alkaloid extracted from traditional Chinese herb, is a potent, selective and reversible acetylcholinesterase (AChE) inhibitor and has been widely used in China for the treatment of Alzheimer's disease (AD). IC50 value:Target: AChEHuperzine A exhibited protective effects against d-gal-induced hepatotoxicity and inflamm-aging by inhibiting AChE activity and via the activation of the cholinergic anti-inflammatory pathway. The huperzine A mechanism might be involved in the inhibition of DAMPs-mediated NF-κB nuclear localization and activation. Huperzine A is a potential therapeutic agent for Alzheimer's disease.

  • CAS Number: 120786-18-7
  • MF: C15H18N2O
  • MW: 242.316
  • Catalog: AChE
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 505.0±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 259.2±30.1 °C

Acetamiprid D3

Acetamiprid-d3  is the deuterium labeled Acetamiprid. Acetamiprid is a neonicotinoid insecticide. Acetamiprid is a nAChR agonist[1].

  • CAS Number: 1353869-35-8
  • MF: C10H8ClD3N4
  • MW: 225.692625334
  • Catalog: nAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

[Arg14,Lys15] Nociceptin

[Arg14,Lys15]Nociceptin is a highly potent and selective NOP receptor agonist, with an EC50 of 1 nM. [Arg14,Lys15]Nociceptin displays high selectivity over opioid receptors, with IC50s of 0.32, 280, >10000 and 1500 nM for NOP (ORL1; OP4), μ, δ and κ receptors, respectively[1].

  • CAS Number: 236098-40-1
  • MF: C82H137N31O22
  • MW: 1909.16000
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Nitrocaramiphen hydrochloride

Nitrocaramiphen hydrochloride is a selective M1 receptor antagonist (Ki: 5.5 nM). Nitrocaramiphen Hydrochloride inhibits the hyperpolarizing effect of muscarine in the muscle fibers[1][2][3].

  • CAS Number: 98636-73-8
  • MF: C18H27ClN2O4
  • MW: 370.87
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

LU-32-176B

LU-32-176B, a GABA transporter 1(GAT1) selective inhibitor, is found to exert a synergistic anticonvulsant action with GAT2 transport inhibitor EF1502. LU-32-176B inhibits neurons, astrocytes and mGAT1 with the IC50 values of 2μM, 1μM, 4μM, respectively[1][2].

  • CAS Number: 770688-66-9
  • MF: C23H24F2N2O2
  • MW: 398.45
  • Catalog: GABA Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Choline hydrogen tartrate

Choline (bitartrate) is an essential nutrient, often associated with the B vitamins but not yet officially defined as a B vitamin[1]. Choline (bitartrate) plays an important role in synthesis of the neurotransmitter acetylcholine[2].

  • CAS Number: 87-67-2
  • MF: C9H19NO7
  • MW: 253.250
  • Catalog: mAChR
  • Density: 1.47 g/cm3
  • Boiling Point: 399.3ºC at 760 mmHg
  • Melting Point: 151-153°C
  • Flash Point: 209.4ºC

YL-0919

YL0919, a novel antidepressant candidate with dual activity as a 5-HT1A receptor agonist and a selective serotonin reuptake inhibitor,the IC50 values of YL-0919 inhibiting the uptake of 5-HT into rat cerebral cortical synaptosomes and human recombinant cells were 1.78±0.34 nM and 1.93±0.18 nM respectively.target: 5-HT1A receptorIC50:1.78±0.34 nM(rat cerebral cortical synaptosomes)IC50:1.93±0.18 nM(human recombinant cells)[1]"In vivo: WAY-100635 completely antagonized the antidepressant-like activity of YL-0919 in both behavioral models, suggesting that activation of the 5-HT1A receptor is critical in the antidepressant-like effect of YL-0919. The administered dose of WAY-100635 ranged from 0.1–0.3 mg/kg, which reportedly has no effect on locomotor activity and only blocks the activation of 5-HT1A receptor.[2]

  • CAS Number: 1339058-04-6
  • MF: C18H23ClN2O2
  • MW: 334.84
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 216 - 218 °C
  • Flash Point: N/A

Foslevodopa

Foslevodopa is a dopamine receptor agonist[1].

  • CAS Number: 97321-87-4
  • MF: C9H12NO7P
  • MW: 277.17
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Timosaponin A3

Timosaponin AIII could inhibit acetylcholinesterase (AChE) activity, with an IC50 of 35.4 μM.

  • CAS Number: 41059-79-4
  • MF: C39H64O13
  • MW: 740.918
  • Catalog: AChE
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 862.8±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 475.6±34.3 °C

Cyclanoline chloride

Cyclanoline (chloride) shows cholinesterase inhibitory activity[1].

  • CAS Number: 17472-50-3
  • MF: C20H24ClNO4
  • MW: 377.86
  • Catalog: AChE
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

UBP141

UBP141 is a GluN2C/2D (NR2C/2D)-preferring receptor antagonist, with Kds of 2.8, 4.2, 14.2, and 19.3 μM for NMDA receptor subtypes: GluN2C, 2D, 2A, and 2B, respectively. UBP141 can induce potent motor impairment in WT mice[1][2].

  • CAS Number: 344768-30-5
  • MF: C21H18N2O5
  • MW: 378.38
  • Catalog: iGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Decamethonium Bromide

Decamethonium Bromide is a nicotinic AChR partial agonist and neuromuscular blocking agent.Target: nAChRDecamethonium (Syncurine) is a depolarizing muscle relaxant or neuromuscular blocking agent, and is used in anesthesia to induce paralysis. Decamethonium, which has a short action time, is similar to acetylcholine and acts as a partial agonist of the nicotinic acetylcholine receptor. In the motor endplate, it causes depolarization, preventing further effects to the normal release of acetylcholine from the presynaptic terminal, and therefore preventing the neural stimulus from affecting the muscle. In the process of binding, decamethonium actually activates (depolarizes) the motor endplate, but since the decamethonium itself is not degraded, the membrane remains depolarized and unresponsive to normal acetylcholine release [1].

  • CAS Number: 541-22-0
  • MF: C16H38Br2N2
  • MW: 418.294
  • Catalog: nAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 263-267 °C(lit.)
  • Flash Point: N/A

RS 127445

RS 127445 is a novel high affinity, selective 5-HT2B receptor antagonist with pKi of 9.5.

  • CAS Number: 199864-86-3
  • MF: C17H17ClFN3
  • MW: 317.78800
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Salfaprodil

Salfaprodil (Neu2000 potassium) is an NR2B-selective and uncompetitive antagonist of N-methyl-D-aspartate (NMDA), and a free radical scavenger. Salfaprodil has excellent neuroprotection against NMDA- and free radical-induced cell death[1][2].

  • CAS Number: 916214-57-8
  • MF: C15H7F7KNO3
  • MW: 421.31
  • Catalog: iGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Isomeranzin

Isomerazin is a coumarin isolated from Poncirus trifoliate Raf., and shows cholinesterase inhibition[1][2].

  • CAS Number: 1088-17-1
  • MF: C15H16O4
  • MW: 260.285
  • Catalog: AChE
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 423.4±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 188.9±28.8 °C

Ajmalicine

Ajmalicine (Raubasine) is found in herbs of Catharanthus roseus, is an antihypertensive drug used in the treatment of high blood pressure, decreases peripheral resistance and blood pressure[1].Ajmalicine (Raubasine) is an adrenolytic drug which preferentially blocks alpha 1-adrenoceptor than alpha 2-adrenoceptor[2].Ajmalicine (Raubasine) is an reversible non-competitive nicotine receptor antagonist with an IC50 of 72.3 μM[3].Ajmalicine (Raubasine) acts preferentially at postsynaptic sites, competitively antagonizes the effect of noradrenaline on postsynaptic alpha-adrenoceptor with a pA2 value of 6.57, blocks the inhibitory effect of clonidine with an pA2 value of 6.2[4].

  • CAS Number: 483-04-5
  • MF: C21H24N2O3
  • MW: 352.427
  • Catalog: Adrenergic Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 524.0±50.0 °C at 760 mmHg
  • Melting Point: 258°C (rough estimate)
  • Flash Point: 270.7±30.1 °C

NMDAR/TRPM4-IN-2

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

  • CAS Number: 2243506-33-2
  • MF: C11H19BrCl2N2
  • MW: 330.09
  • Catalog: ERK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Vazegepant

Vazegepant is the first intranasal CGRP receptor antagonist for the study the acute research of migraine[1][2].

  • CAS Number: 1337918-83-8
  • MF: C36H46N8O3
  • MW: 638.80
  • Catalog: CGRP Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 933.7±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 518.5±34.3 °C

Oxidopamine hydrochloride

Oxidopamine hydrochloride is a neurotoxic synthetic organic compound, selectively destroys dopaminergic and noradrenergic neurons in the brain.

  • CAS Number: 28094-15-7
  • MF: C8H12ClNO3
  • MW: 205.63900
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: 406ºC at 760 mmHg
  • Melting Point: 232-233ºC (dec.)(lit.)
  • Flash Point: 199.3ºC

Talnetant

Talnetant (SB 223412) is a potent and selective NK3 receptor antagonist (ki=1.4 nM, hNK-3-CHO); 100-fold selective for the hNK-3 versus hNK-2 receptor, with no affinity for the hNK-1 at concentrations up to 100 uM.IC50 Value: 1.4 nM (hNK-3-CHO binding Ki) [1]Target: NK3 receptorin vitro: In vitro studies demonstrated that 53 is a potent functional antagonist of the hNK-3 receptor (reversal of senktide-induced contractions in rabbit isolated iris sphincter muscles and reversal of NKB-induced Ca2+ mobilization in CHO cells stably expressing the hNK-3 receptor), while in vivo this compound showed oral and intravenous activity in NK-3 receptor-driven models (senktide-induced behavioral responses in mice and senktide-induced miosis in rabbits) [1]. Talnetant has high affinity for recombinant human NK3 receptors (pKi 8.7) and demonstrates selectivity over other neurokinin receptors (pKi NK2 = 6.6 and NK1<4). In native tissue-binding studies, talnetant displayed high affinity for the guinea pig NK3 receptor (pKi 8.5) [3].in vivo: Rectal barostat tests were performed on 102 healthy volunteers, randomized to receive either oral talnetant 25 or 100 mg or placebo over 14-17 days [2]. Talnetant (3-30 mg/kg i.p.) significantly attenuated senktide-induced 'wet dog shake' behaviors in the guinea pig in a dose-dependent manner. Microdialysis studies demonstrated that acute administration of talnetant (30 mg/kg i.p.) produced significant increases in extracellular dopamine and norepinephrine in the medial prefrontal cortex and attenuated haloperidol-induced increases in nucleus accumbens dopamine levels in the freely moving guinea pigs [3].Toxicity: Talnetant had no effect on rectal compliance, sensory thresholds or intensity ratings compared with placebo [2].Clinical trial: Study Of Talnetant Versus Placebo And Risperidone In Schizophrenia. Phase 2

  • CAS Number: 174636-32-9
  • MF: C25H22N2O2
  • MW: 382.45400
  • Catalog: Neurokinin Receptor
  • Density: 1.212g/cm3
  • Boiling Point: 580.4ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 304.8ºC

SB 204741

SB 204741 is a selective and high affinity 5-HT2B antagonist with a pKi value of 7.1[1].

  • CAS Number: 152239-46-8
  • MF: C14H14N4OS
  • MW: 286.35200
  • Catalog: 5-HT Receptor
  • Density: 1.38g/cm3
  • Boiling Point: 335.9ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 157ºC

Carpro-AM1

Carpro-AM1 is a dual-acting FAAH/substrate-selective COX inhibitor with an IC50 value of 94 nM for FAAH[1].

  • CAS Number: 2499489-76-6
  • MF: C21H18ClN3O
  • MW: 363.84
  • Catalog: COX
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CP465022 HCl

CP-465022 is a potent, and selective noncompetitive AMPA receptor antagonist with anticonvulsant activity. CP-465022 is against Kainate-induced response with an IC50 of 25 nM in rat cortical neurons. CP-465022 provides a new tool to investigate the role of AMPA receptors in physiological and pathophysiological processes[1][2].

  • CAS Number: 199655-36-2
  • MF: C26H24ClFN4O
  • MW: 462.95
  • Catalog: iGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Temiverine hydrochloride

Temiverine hydrochloride is a synthesized drug that is expected to have anticholinergic action.

  • CAS Number: 136529-33-4
  • MF: C24H36ClNO3
  • MW: 422.000
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Rimacalib

Rimacalib is a Ca2+/calmodulin-dependent protein kinase II (CaMKII) inhibitor, with IC50s of ~1 μM for CaMKIIα to ~30 μM for CaMKIIγ.

  • CAS Number: 215174-50-8
  • MF: C22H23FN4O2
  • MW: 394.44200
  • Catalog: CaMK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SB 205384

SB-205384 is a GABAA receptor modulator. The primary effect of SB-205384 on GABAA-activated currents is a prolonged response decay half-life upon removal of the agonist[1].

  • CAS Number: 160296-13-9
  • MF: C17H18N2O3S
  • MW: 330.40
  • Catalog: GABA Receptor
  • Density: 1.38g/cm3
  • Boiling Point: 565.3ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 295.7ºC

Myosmine

Myosmine, a specific tobacco alkaloid in nuts and nut products, has low affinity for a4b2 nicotinic acetylcholinergic receptors (nAChR) with a Ki of 3300 nM[1][2].

  • CAS Number: 532-12-7
  • MF: C9H10N2
  • MW: 146.189
  • Catalog: nAChR
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 244.7±22.0 °C at 760 mmHg
  • Melting Point: 42-44°C
  • Flash Point: 101.8±22.3 °C