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
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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SB 218795

SB 218795 is a potent and selective non-peptide NK3 receptor antagonist, with a Ki 13 nM for hNK3. SB 218795 shows about 90-fold and 7000-fold selectivity for hNK3 over hNK2 and hNK1, respectively. SB 218795 can inhibit NK3 receptor-mediated pupillary constriction of the rabbit[1][2].

  • CAS Number: 174635-53-1
  • MF: C25H20N2O3
  • MW: 396.44
  • Catalog: Neurokinin Receptor
  • Density: 1.237g/cm3
  • Boiling Point: 623.7ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 331ºC

α-NETA

α-NETA is a potent and noncompetitive choline acetyltransferase (ChA) inhibitor with an IC50 of 9 μM. α-NETA is a potent ALDH1A1 (IC50=0.04 µM) and chemokine-like receptor-1 (CMKLR1) antagonist. α-NETA weakly inhibits cholinesterase (ChE; IC50=84 µM) and acetylcholinesterase (AChE; IC50=300 µM). α-NETA has anti-cancer activity[1][2].

  • CAS Number: 115066-04-1
  • MF: C16H20INO
  • MW: 369.25
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(D-Arg1,D-Pro2,D-Trp7·9,Leu11)-Substance P

(D-Arg1,D-Pro2,D-Trp7,9,L-Leu11)-Substance P is a neuropeptide Substance P (HY-P0201) antagonist[1].

  • CAS Number: 84676-91-5
  • MF: C75H108N20O13
  • MW: 1497.79000
  • Catalog: Neurokinin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Aprepitant

Aprepitant (MK-0869) is a selective and high-affinity neurokinin 1 receptor antagonist with a Kd of 86 pM.

  • CAS Number: 170729-80-3
  • MF: C23H21F7N4O3
  • MW: 534.427
  • Catalog: Neurokinin Receptor
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: 75-76 °C(lit.)
  • Flash Point: N/A

3-O-Methyldopa D3

3-O-Methyldopa D3 (3-Methoxy-L-tyrosine D3) is deuterium labeled 3-O-Methyldopa. 3-O-Methyldopa is a metabolite of L-DOPA which is formed by catechol-O-methyltransferase (COMT). 3-O-Methyldopa competitively inhibits the pharmacodynamics of l-DOPA and dopamine[1].

  • CAS Number: 586954-09-8
  • MF: C10H10D3NO4
  • MW: 214.23300
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

M1/M2/M4 muscarinic agonist 1

M1/M2/M4 muscarinic agonist 1 (Compound 42) is a muscarinic M4/M1/M2 agonist with EC50 values of 6.5, 26 and 210 nM for M4/M1/M2, respectively. M1/M2/M4 muscarinic agonist 1 can be used for research on mental diseases, such as schizophrenia, delusion, etc[1].

  • CAS Number: 2640109-42-6
  • MF: C24H34N2O3
  • MW: 398.54
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Solifenacin D5 hydrochloride

Solifenacin D5 hydrochloride is a deuterium labeled Solifenacin hydrochloride. Solifenacin hydrochloride is a muscarinic receptor antagonist with pKis of 7.6, 6.9 and 8.0 for M1, M2 and M3 receptors, respectively[1].

  • CAS Number: 1426174-05-1
  • MF: C23H22D5ClN2O2
  • MW: 403.96
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cycloleucine

Cycloleucine is a specific inhibitor of S-adenosyl-methionine mediated methylation. Cycloleucine is antagonist of NMDA receptor associated glycine receptor, with a Ki of 600 μM. Cycloleucine is also a competitive inhibitor of ATP: L-methionine-S-adenosyl transferase in vitro. Cycloleucine has anxiolytic and cytostatic effects[1][2][3][4].

  • CAS Number: 52-52-8
  • MF: C6H11NO2
  • MW: 129.157
  • Catalog: iGluR
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 256.1±23.0 °C at 760 mmHg
  • Melting Point: 320 °C (dec.)(lit.)
  • Flash Point: 108.7±22.6 °C

Quetiapine Fumarate

Quetiapine fumarate is an atypical antipsychotic used in the treatment of schizophrenia, bipolar I mania, bipolar II depression, bipolar I depression.IC50 value: Target: 5-HT ReceptorQuetiapine is indicated for the treatment of schizophrenia as well as for the treatment of acute manic episodes associated with bipolar I disorder. The antipsychotic effect of quetiapine is thought by some to be mediated through antagonist activity at dopamine and serotonin receptors. Specifically the D1 and D2 dopamine, the alpha 1 adrenoreceptor and alpha 2 adrenoreceptor, and 5-HT1A and 5-HT2 serotonin receptor subtypes are antagonized. Quetiapine also has an antagonistic effect on the histamine H1 receptor.

  • CAS Number: 111974-72-2
  • MF: C46H54N6O8S2
  • MW: 883.1
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: 556.5ºC at 760 mmHg
  • Melting Point: 174-176°C
  • Flash Point: 290.4ºC

Mesdopetam

Mesdopetam (IRL790) is a dopamine D3 receptor antagonist (Ki=90 nM; IC50=9.8 μM for human recombinant D3 receptor) with psychomotor stabilizing properties. Mesdopetam is used for the research of motor and psychiatric complications in Parkinson disease[1][2].

  • CAS Number: 1403894-72-3
  • MF: C12H18FNO3S
  • MW: 275.34
  • Catalog: Dopamine Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 428.5±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 212.9±28.7 °C

CS-003 Free base

CS-003 Free base (CS-003), a triple tachykinin receptor antagonist, shows high affinities for human (Neurokinin) NK1, NK2 and NK3 receptors with Ki values of 2.3 nM, 0.54 nM and 0.74 nM, respectively. CS-003 Free base (CS-003) has therapeutic efficacy on respiratory diseases associated with neurokinins.

  • CAS Number: 191672-52-3
  • MF: C34H38Cl2N2O6S
  • MW: 673.65
  • Catalog: Neurokinin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Fosaprepitant dimeglumine salt

Fosaprepitant dimeglumine(MK-0517) is a neurokinin-1 receptor antagonist for the prevention of chemotherapy-induced nausea and vomiting.IC50 Value:Target: NK1 receptorin vitro: Fosaprepitant (also known as MK-0517 and L-758,298) is a water-soluble phosphoryl prodrug for aprepitant, which, when administered intravenously, is converted to aprepitant within 30 min of intravenous administration via the action of ubiquitous phosphatases. Owing to the rapid conversion offosaprepitant to the active form (aprepitant), fosaprepitant 115 mg provided the same aprepitant exposure in terms of AUC as aprepitant 12 mg orally, and fosaprepitant is expected to provide a correspondingly similar antiemetic effect as aprepitant [1]. in vivo: Fosaprepitant is well tolerated with mild to moderate venous irritation being the only additional toxicity to those seen with oral aprepitant, and that is a function of dose, concentration, and infusion rate [2]. Patients receiving cisplatin ≥ 70 mg/m(2) for the first time received ondansetron and dexamethasone with a standard aprepitant regimen (125 mg on day 1, 80 mg on day 2, 80 mg on day 3) or a single-dose fosaprepitant regimen (150 mg on day 1) [3]. Single-dose fosaprepitant used in combination with granisetron and dexamethasone was well-tolerated and effective in preventing chemotherapy-induced nausea and vomiting in patients receiving highly emetogenic cancer chemotherapy, including high-dose cisplatin [4].

  • CAS Number: 265121-04-8
  • MF: C37H56F7N6O16P
  • MW: 1004.83000
  • Catalog: Neurokinin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Rabies Virus Matrix Protein Fragment(RV-MAT)

Rabies Virus Matrix Protein Fragment (RV-MAT) is a polypeptide. Rabies Virus Matrix Protein Fragment targets the acetylcholine receptor (AChR) that exists on the cell surface[1].

  • CAS Number: 1023648-37-4
  • MF: C135H232N44O47S
  • MW: 3255.64
  • Catalog: nAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Razpipadon

Razpipadon ((-)-PW0464), an aromatic compound, is a dopamine receptor partial agonist. Razpipadon can be used in the study of dopamine D1 ligand-mediated related psychiatric disorders[1][2].

  • CAS Number: 1643489-35-3
  • MF: C19H17F2N3O4
  • MW: 389.35
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BuChE-IN-TM-10

BuChE-IN-TM-10 (TM-10) is a potent butyrylcholinesterase (BuChE) inhibitor, with an IC50 of 8.9 nM. BuChE inhibitor 1 inhibits and disaggregates self-induced Aβ aggregation, exhibiting potent antioxidant activity and good blood-brain barrier (BBB) penetration. Has potential to treat Alzheimer’s disease[1].

  • CAS Number: 2313524-95-5
  • MF: C32H38N2O3
  • MW: 498.66
  • Catalog: AChE
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Sofpironium bromide

Sofpironium bromide (BBI 4000) is an anticholinergic agent used in the study of primary axillary hyperhidrosis (PAH). Sofpironium bromide reduces sweating by inhibiting M3 muscarinic receptors in eccrine glands at the application site. Sofpironium bromide also has a high afnity for the M1, M2, M4 and M5 subtypes[1].

  • CAS Number: 1628106-94-4
  • MF: C22H32BrNO5
  • MW: 470.40
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tropicamide

Tropicamide is an anticholinergic and a muscarinic receptor subtype M4-preferring antagonist .Target: mAChRTropicamide is an antimuscarinic drug that produces short acting mydriasis (dilation of the pupil) and cycloplegia when applied as eye drops. It is used to allow better examination of the lens, vitreous humor, and retina. Due to its relatively short duration of effect (4-8 hours), it is typically used during eye examinations such as the dilated fundus examination, but it may also be used before or after eye surgery. Cycloplegic drops are often also used to treat anterior uveitis, decreasing risk of posterior synechiae and decreasing inflammation in the anterior chamber of the eye [1-3].

  • CAS Number: 1508-75-4
  • MF: C17H20N2O2
  • MW: 284.353
  • Catalog: mAChR
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 492.8±45.0 °C at 760 mmHg
  • Melting Point: 98 °C
  • Flash Point: 251.8±28.7 °C

Alverine citrate

Alverine citrate is a 5-HT1A receptor antagonist, with an IC50 of 101 nM.

  • CAS Number: 5560-59-8
  • MF: C26H35NO7
  • MW: 473.55900
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: 358.8ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 174.4ºC

YM-46303

YM-46303 is an mAChR antagonist which exhibits the highest affinities for M1 and M3 receptors, and selectivity for M3 over M2 receptor.

  • CAS Number: 171722-81-9
  • MF: C20H23ClN2O2
  • MW: 358.86
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

M1 ligand 1

M1 ligand 1 (compound 3b-b) is a muscarinic acetylcholine receptor M1 ligand. M1 ligand 1 is a N-desmethyl congener of arecoline derivative. M1 ligand 1 can be used as PET (positron emission tomography) radiotracer[1].

  • CAS Number: 2479356-53-9
  • MF: C20H21NO2
  • MW: 307.39
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Naspm

Naspm (1-Naphthyl acetyl spermine), a synthetic analogue of Joro spider toxin, is a calcium permeable AMPA (CP-AMPA) receptors antagonist.

  • CAS Number: 122306-11-0
  • MF: C22H34N4O
  • MW: 370.53
  • Catalog: iGluR
  • Density: 1.062g/cm3
  • Boiling Point: 608.9ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 322.1ºC

Epiboxidine hydrochloride

Epiboxidine is a potent and selective neural nAChR agonist with Kis of 0.46 nM and 1.2 nM for rat and human α4β2 nAChRs, respectively. Epiboxidine is a methylisoxazole analog of the alkaloid Epibatidine, and is also an analog of another nAChR agonist, ABT 418[1].

  • CAS Number: 188895-96-7
  • MF: C10H14N2O
  • MW: 178.23
  • Catalog: nAChR
  • Density: 1.13g/cm3
  • Boiling Point: 313.1ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 143.2ºC

Fanapanel hydrate

Fanapanel hydrate (ZK200775 hydrate) is a highly selective AMPA/kainate antagonist with little activity against NMDA; have Ki values of 3.2 nM, 100 nM, and 8.5 μM against quisqualate, kainate, and NMDA, respectively.

  • CAS Number: 1255517-78-2
  • MF: C14H17F3N3O7P
  • MW: 427.270
  • Catalog: iGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

LY 2886721 Hydrochloride

LY2886721 hydrochloride is a potent, selective and orally active beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitor with an IC50 of 20.3 nM for recombinant human BACE1. LY2886721 hydrochloride is selectivity against cathepsin D, pepsin, and renin, but lacking selectivity against BACE2 (IC50 of 10.2 nM). LY2886721 hydrochloride can across blood-brain barrier and has the potential for Alzheimer's disease treatment[1].

  • CAS Number: 1262036-49-6
  • MF: C18H17ClF2N4O2S
  • MW: 426.87
  • Catalog: Beta-secretase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

LY2624803

LY2624803 is a novel potent histamine H1 and 5HT-2A receptor modulator in the pipeline for treating insomnia. Sleep Disorder Phase 2 Discontinued

  • CAS Number: 879409-35-5
  • MF: C22H25N3O3
  • MW: 379.452
  • Catalog: 5-HT Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 554.3±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 289.0±32.9 °C

Memoquin

Memoquin is an anti-amyloid and anti-oxidant multi-target-directed ligand. Memoquin is an orally active inhibitor of BACE-1 and AChE with IC50 values of 108 and 1.55 nM, respectively. Memoquin is a cognitive enhancer that prevents the Aβ-induced neurotoxicity mediated by oxidative stress. Memoquin can be used for the research of Alzheimer’s disease (AD)[1][2].

  • CAS Number: 616885-87-1
  • MF: C38H56N4O4
  • MW: 632.876
  • Catalog: AChE
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 722.9±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 391.0±32.9 °C

OSU 6162 hydrochloride

(-)-OSU6162 (PNU96391) hydrochloride is a dopamine stabilizer. (-)-OSU6162 hydrochloride acts as partial agonist at 5-HT2A and is a dopamine D2 antagonist. (-)-OSU6162 hydrochloride can be used for the research of aggression and irritability[1][2].

  • CAS Number: 156907-84-5
  • MF: C15H24ClNO2S
  • MW: 317.87
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: 436.5ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 217.8ºC

BChE-IN-9

BChE-IN-9 (Azepano-11-deoxo-glycyrrhetol) is a mixed type BChE inhibitor with a Ki of 0.21 µM[1].

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

BML-278

Flavoxate is a potent and competitive phosphodiesterase (PDE) inhibitor. Flavoxate is an antispasmodic agent and muscarinic mAChR antagonist. Flavoxate shows moderate calcium antagonistic activity and local anesthetic effect. Flavoxate can be used for the research of overactive bladder (OAB) and lower urinary tract infections[1][2].

  • CAS Number: 15301-69-6
  • MF: C24H25NO4
  • MW: 391.460
  • Catalog: mAChR
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 564.1±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 294.9±30.1 °C

5-HT6/7 antagonist 1

5-HT6/7 antagonist 1 is a multifunctional ligand that antagonizes 5-HT6/7/2A and D2 receptors, without interacting with M1 receptors and hERG channels.

  • CAS Number: 131999-28-5
  • MF: C22H20FN3O3
  • MW: 393.41
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A