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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Apoptosis >
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Autophagy >
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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)
Membrane Transporter/Ion Channel >
ATP Synthase BCRP Calcium Channel CFTR Chloride Channel CRAC Channel CRM1 EAAT2 GABA Receptor GlyT HCN Channel iGluR Monoamine Transporter Monocarboxylate Transporter Na+/Ca2+ Exchanger Na+/HCO3- Cotransporter Na+/K+ ATPase nAChR NKCC P-glycoprotein P2X Receptor Potassium Channel Proton Pump SGLT Sodium Channel TRP Channel URAT1
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 >
NF-κB IKK Keap1-Nrf2 MALT1
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Akt AMPK ATM/ATR DNA-PK GSK-3 MELK mTOR PDK-1 PI3K PI4K PIKfyve PTEN
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Donitriptan monohydrochloride

Donitriptan hydrochloride (F-11356) is a potent, high efficacy agonist at 5-HT1B/1D receptors with pKis of 9.4 and 9.3, respectively[1].

  • CAS Number: 170911-68-9
  • MF: C23H26ClN5O2
  • MW: 439.94
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: 727.1ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 393.6ºC

Fesoterodine

Fesoterodine is an orally active, nonsubtype selective, competitive muscarinic receptor (mAChR) antagonist with pKi values of 8.0, 7.7, 7.4, 7.3, 7.5 for M1, M2, M3, M4, M5 receptors, respectively. Fesoterodine is used for the overactive bladder (OAB)[1][2].

  • CAS Number: 286930-02-7
  • MF: C26H37NO3
  • MW: 412.58500
  • Catalog: mAChR
  • Density: 1.043
  • Boiling Point: 518.9ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 267.6ºC

Yoda 1

GlyT2-IN-1 is a glycine transporters GLYT2 inhibitor.Target: GLYT2The Glycine Transporter GlyT2 Controls the Dynamics of Synaptic Vesicle Refilling in Inhibitory Spinal Cord Neurons. GlyT2-IN-1 is a novel agonist of the mechanotransduction channel Piezo1, eliciting Ca2+ flux in Piezo1- but not vector-transfected cells.

  • CAS Number: 448947-81-7
  • MF: C13H8Cl2N4S2
  • MW: 355.265
  • Catalog: GlyT
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 538.4±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 279.4±32.9 °C

Dolasetron (Mesylate hydrate)

Dolasetron(MDL-73147) is a serotonin 5-HT3 receptor antagonist used to treat nausea and vomiting following chemotherapy.

  • CAS Number: 878143-33-0
  • MF: C20H26N2O7S
  • MW: 438.49
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 178 °C
  • Flash Point: N/A

S 24795

S 24795 is a partial agonist of α7 nAChR and improves mnemonic function in aged mice for the treatment of aging-related memory disturbances[1].

  • CAS Number: 304679-75-2
  • MF: C14H13BrINO
  • MW: 418.06800
  • Catalog: nAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(R,R)-Palonosetron Hydrochloride

(R,R)-Palonosetron Hydrochloride is the active enantiomer of Palonosetron.

  • CAS Number: 135729-75-8
  • MF: C19H25ClN2O
  • MW: 332.87
  • Catalog: 5-HT Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 470.4±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 209.5±21.1 °C

Multitarget AD inhibitor-1

Multitarget AD inhibitor-1 is a selective and reversible butyrylcholinesterase (BuChE) inhibitor with IC50s of 7.22 μM and 1.55 μM for hBuChE and eqBuChE, respectively. Multitarget AD inhibitor-1 inhibits β-secretase (IC50hBACE-1=41.60 μM), amyloid β aggregation (IC50 Aβ=3.09 μM), tau aggregation (55% at 10 μM). Multitarget AD inhibitor-1, a diphenylpropylamine derivative, has the potential for multifunctional disease-modifying anti-Alzheimer’s[1].

  • CAS Number: 2205015-77-4
  • MF: C29H38N2O
  • MW: 430.62
  • Catalog: Beta-secretase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SR 140333

Nolpitantium (SR140333) is a potent, selective, competitive, non-peptide tachykinin NK1 receptor antagonist. Nolpitantium blocks the activation of rat thalamic neurons after nociceptive stimulation[1].

  • CAS Number: 153050-21-6
  • MF: C37H45Cl3N2O2
  • MW: 656.12
  • Catalog: Neurokinin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Coclaurine

Coclaurine is a class of tetrahydroisoquinoline alkaloids isolated from Sarcopetalum harveyanum. Coclaurine is a nicotinic acetylcholine receptor (nAChRs) antagonist[1][2].

  • CAS Number: 486-39-5
  • MF: C17H19NO3
  • MW: 285.338
  • Catalog: nAChR
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 496.9±45.0 °C at 760 mmHg
  • Melting Point: 220-221°
  • Flash Point: 254.3±28.7 °C

σ1 Receptor/μ Opioid receptor modulator 1

σ1 Receptor/μ Opioid receptor modulator 1 (Compound 44) is a potent σ1 receptor antagonist and μ opioid receptor agonist with Kis of 1.86 nM and 2.1 nM, respectively.σ1 Receptor/μ Opioid receptor modulator 1 exhibits potent analgesic activity. σ1 Receptor/μ Opioid receptor modulator 1 can be used for the research of neuropathic pain[1].

  • CAS Number: 2412700-00-4
  • MF: C24H31FN2O2
  • MW: 398.51
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Odapipam

Odapipam (NNC 756) is a selective, high affinity and benzazepine dopamine D1 receptor antagonist with a Kd of 0.18 nM. Odapipam is also a superior positron emission tomography (PET) radiotracer[1][2].

  • CAS Number: 131796-63-9
  • MF: C19H20ClNO2
  • MW: 329.82100
  • Catalog: Dopamine Receptor
  • Density: 1.269g/cm3
  • Boiling Point: 460.4ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 232.2ºC

RO 4938581

RO 4938581 is a potent and selective GABAA α5 inverse agonist, with a Ki of 4.6 nM for GABAA α5β3γ2a, and shows a lower affinity at α1β3γ2a, α2β3γ2a, α3β3γ2a (Ki, 174, 185, 80 nM, respectively); RO 4938581 is used in the research of cognitive dysfunction.

  • CAS Number: 883093-10-5
  • MF: C13H8BrF2N5
  • MW: 352.137
  • Catalog: GABA Receptor
  • Density: 1.9±0.1 g/cm3
  • Boiling Point: 559.8±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 292.4±32.9 °C

MRK-898

MRK-898 is an orally active GABA(A) receptor modulator. MRK-898 binds to α1, α2, α3 or α5 subunit of GABA(A) receptor with Ki values of 1.2 nM, 1.0 nM, 0.73 nM, and 0.50 nM, respectively. However, α1-containing GABA(A) receptors are identified as the "sedative" and α2- and/or α3-containing receptors as the "anxiolytic" subtype(s)[1].

  • CAS Number: 461450-30-6
  • MF: C20H9F5N4
  • MW: 400.30
  • Catalog: GABA Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AMG 8718

AMG-8718 is a potent, selective and orally active BACE1 inhibitor with IC50 values of 0.0007, 0.005 µM for BACE1 and BACE2, respectively. AMG-8718 significantly decreases Aβ40 levels in the CSF and brain[1].

  • CAS Number: 1215868-94-2
  • MF: C25H19FN4O3
  • MW: 442.442
  • Catalog: Beta-secretase
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 673.7±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 361.2±34.3 °C

Quetiapine D4 fumarate

Quetiapine D4 fumarate is the deuterium labeled Quetiapine, which is an atypical antipsychotic.

  • CAS Number: 1287376-15-1
  • MF: C25H25D4N3O6S
  • MW: 503.60
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 72-780C
  • Flash Point: N/A

Pindolol-d7

Pindolol-d7 (LB-46-d7) is the deuterium labeled Pindolol. Pindolol (LB-46) is a nonselective β-blocker with partial beta-adrenergic receptor agonist activity, also functions as a 5-HT1A receptor weak partial antagonist (Ki=33 nM)[1][2].

  • CAS Number: 1185031-19-9
  • MF: C14H13D7N2O2
  • MW: 255.36400
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(±)-trans-10,11-Dihydroxy-5,6,6a,7,8,12b-hexahydrobenzo[a]phenanthridine hydrochloride

Dihydrexidine hydrochloride (DAR-0100 hydrochloride) is a high potent, selective and full efficacy D1-like dopamine receptor (D1/D5) agonist, with an IC50 of 10 nM for D1 receptor. Dihydrexidine hydrochloride exhibits potent antiparkinsonian activity[1][2][3][4].

  • CAS Number: 137417-08-4
  • MF: C17H18ClNO2
  • MW: 303.78
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MAO-B-IN-12

MAO-B-IN-12 (Compound 16c) is a potent monoamine oxidase B (MAO-B) inhibitor with an IC50 of 1.3 μM. MAO-B-IN-12 shows a neuroprotective activity[1].

  • CAS Number: 2394733-97-0
  • MF: C22H30O4
  • MW: 358.47
  • Catalog: Monoamine Oxidase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Dopamine D3 receptor ligand-4

Dopamine D3 receptor ligand-4 (compound 6) is a potent and selective dopamine D3 receptor ligand, with a Ki of 0.5 nM. Dopamine D3 receptor ligand-4 shows high level of selectivity for D3 over D2 (Ki=7.43 nM). Dopamine D3 receptor ligand-4 can be used for the research of Cocaine use disorder[1].

  • CAS Number: 2376333-77-4
  • MF: C26H28N4OS
  • MW: 444.59
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

F 14679

F 14679 is a prototypical 5-HT1A agonist with a pKi of 10.23. F 14679 induces large Ca2+ responses[1].

  • CAS Number: 208109-38-0
  • MF: C21H25ClF2N4O
  • MW: 422.90
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

RS-127445

RS-127445 is a selective, high affinity, orally bioavailable 5-HT2B receptor antagonist with a pKi of 9.5. RS-127445 shows 1000 fold selectivity for this receptor as compared to numerous other receptor and ion channel binding sites[1].

  • CAS Number: 199864-87-4
  • MF: C17H17ClFN3
  • MW: 317.788
  • Catalog: 5-HT Receptor
  • Density: 1.213g/cm3
  • Boiling Point: 472.8ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 239.8ºC

AChE/BuChE/MAO-B-IN-1

AChE/BuChE/MAO-B-IN-1 (compound 19) is an inhibitor of human acetyl- (hAChE), butyrylcholinesterase (hBuChE) and monoamine oxidase-B (hMAO-B) with IC50s of 4.8 μM, 13.7 μM, and 1.11 μM, respectively. AChE/BuChE/MAO-B-IN-1 also exhibits high affinity to both the σ1 and σ2 receptors with Ki values of 42.8 nM (human σ1 receptor) and 191 nM (rat σ2 receptor), respectively. AChE/BuChE/MAO-B-IN-1 can be used for Alzheimer’s disease research[1].

  • CAS Number: 2834758-29-9
  • MF: C17H23NO3
  • MW: 289.37
  • Catalog: AChE
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Fesoterodine Fumarate

Fesoterodine Fumarate is an antimuscarinic agent and is rapidly de-esterified to its active metabolite 5-hydroxymethyl tolterodine that is a muscarinic receptor antagonist.IC50 value:Target: mAChRFesoterodine has the advantage of allowing more flexible dosage than other muscarinic antagonists. Its tolerability and side effects are similar to other muscarinic antagonists and as a new drug seems unlikely to make great changes in practices of treatment for overactive bladder.

  • CAS Number: 286930-03-8
  • MF: C30H41NO7
  • MW: 527.649
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: 518.9ºC at 760 mmHg
  • Melting Point: 72-78ºC
  • Flash Point: 267.6ºC

AP521

AP521 is an agonist of human 5-HT1A receptor with an IC50 of 94 nM.

  • CAS Number: 151227-08-6
  • MF: C20H19ClN2O3S
  • MW: 402.895
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Fenoldopam

Fenoldopam(SKF 82526) is a drug and synthetic benzazepine derivative which acts as a selective D1 receptor partial agonist.Target: D1 ReceptorFenoldopam is a selective dopamine-1 (DA1) agonist with natriuretic/diuretic properties. Fenoldopam stimulated cAMP accumulation in LLC-PK1 cells in a dose-dependent manner, an effect which could be blocked by the DA1-selective antagonist Sch 23390. Although fenoldopam was more potent than DA (EC50 55.5 +/- 7.75 nM vs. 1.65 +/- 0.64 microM) in stimulating cAMP accumulation in LLC-PK1 cells, the maximum stimulation obtained by fenoldopam was only 37% of the maximum stimulation obtained by DA(Emax 13.0 +/- 2.95 pmol/mg of protein vs. 35.6 +/- 10.19 pmol/mg of protein) [1]. Fenoldopam is a selective dopamine1 (DA1) receptor agonist. Most of the DA1 receptor agonist activity of fenoldopam resides in the R-enantiomer, which also shows weaker alpha 2-adrenoceptor antagonist activity Fenoldopam produces vasodilation in vascular beds that are rich in vascular DA1 receptors [2].

  • CAS Number: 67227-56-9
  • MF: C16H16ClNO3
  • MW: 305.756
  • Catalog: Dopamine Receptor
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 522.6±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 269.9±30.1 °C

Cariprazine D8

Cariprazine D8 (RGH-188 D8) is a deuterium labeled Cariprazine. Cariprazine is a novel antipsychotic drug candidate that exhibits high affinity for the D3 (Ki=0.085 nM) and D2 (Ki=0.49 nM) receptors, and moderate affinity for the 5-HT1A receptor (Ki=2.6 nM).

  • CAS Number: 1308278-50-3
  • MF: C21H32Cl2N4O
  • MW: 435.5
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A