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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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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Rosmarinic acid

Rosmarinic acid (RA) is a widespread phenolic ester compound in the plants. Rosmarinic acid inhibits MAO-A, MAO-B and COMT enzymes with IC50s of 50.1, 184.6 and 26.7 μM, respectively.

  • CAS Number: 20283-92-5
  • MF: C18H16O8
  • MW: 360.315
  • Catalog: Monoamine Oxidase
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 694.7±55.0 °C at 760 mmHg
  • Melting Point: 171-175 °C(lit.)
  • Flash Point: 254.5±25.0 °C

Tacrine

Tacrine is a potent acetylcholinesterse (AChE) inhibitor (IC50=109 nM), also acting as a CYP1A2 substrate drug. Tacrine exhibits certain hepatotoxicity in some individuals. Tacrine can be used for researching Alzheimer's disease (AD)[1][2][3].

  • CAS Number: 321-64-2
  • MF: C13H14N2
  • MW: 198.264
  • Catalog: AChE
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 353.8±42.0 °C at 760 mmHg
  • Melting Point: 283-284ºC
  • Flash Point: 167.8±27.9 °C

VU 0255035

VU 0255035 is a highly selective, competitive and brain penetrant muscarinic M1 receptor antagonist with an IC50 of 130 nM. VU 0255035 reduces pilocarpine-induced seizures in mice. VU0255035 is used to examine the role of the M1 receptor in diverse situations[1].

  • CAS Number: 1135243-19-4
  • MF: C18H20N6O3S2
  • MW: 432.52000
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: 689.3±65.0°C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: N/A

ADL5859 HCl

ADL5859 is a δ-opioid receptor agonist with Ki of 0.8 nM, selectivity against opioid receptor κ, μ, and weak inhibitory activity at the hERG channel. IC50 value: 0.8 nM(Ki)Target: δ-opioid receptorADL-5859 (ADL5859) is an δ-opioid receptor agonist (Ki=0.84 nM, EC50=20 nM). ADL-5859 (ADL5859) is an agonist agent that selectively stimulates the δ-opioid receptor with potential application in a wide range of inflammatory, neuropathic and acute pain conditions. In addition, Delta agonists are thought to modulate other biological processes that may manifest themselves in disease states or conditions such as overactive bladder and depression.ADL-5859 (ADL5859) is useful for inflammatory, neuropathic and acute pain conditions.

  • CAS Number: 850173-95-4
  • MF: C24H29ClN2O3
  • MW: 428.952
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

5-HT6/5-HT2A receptor ligand-2

5-HT6/5-HT2A receptor ligand-2 (compound 42) is a brain-penetrant dual 5-HT6/5-HT2A receptor antagonist, with a Ki of 25 nM and 32 nM, respectively. 5-HT6/5-HT2A receptor ligand-2 shows pro-cognitive properties[1].

  • CAS Number: 2411088-16-7
  • MF: C20H18FN3O2
  • MW: 351.37
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A
  • CAS Number: 186142-28-9
  • MF: C50H78N14O19
  • MW: 1179.237
  • Catalog: Beta-secretase
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Pimethixene

Pimethixene is an antihistamine and anticholinergic agent, that is often used to treat hyperactivity, anxiety, sleep disorders, and allergy.

  • CAS Number: 314-03-4
  • MF: C19H19NS
  • MW: 293.42600
  • Catalog: Histamine Receptor
  • Density: 1.192g/cm3
  • Boiling Point: 439.7ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 219.7ºC

Zanapezil free base

Zanapezil (TAK-147) free base is a potent, reversible and selective acetylcholine esterase (AChE) inhibitor. Zanapezil free base shows a potent and reversible inhibition of AChE activity in homogenates of the rat cerebral cortex (IC50=51.2 nM). Zanapezil free base shows a moderate inhibition of muscarinic M1 and M2 receptor binding with Ki values of 234 and 340 nM, respectively. Zanapezil free base can be used for the research of early stages of Alzheimer's disease (AD)[1].

  • CAS Number: 142852-50-4
  • MF: C25H32N2O
  • MW: 376.53
  • Catalog: AChE
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

gamma-secretase modulator 1

γ-secretase inhibitior-1 is a gamma-secretase modulator, γ-secretase inhibitior-1 is useful for Alzheimer's disease.

  • CAS Number: 1172637-87-4
  • MF: C24H24N4OS
  • MW: 416.53900
  • Catalog: γ-secretase
  • Density: 1.3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tiagabine hydrochloride

Tiagabine hydrochloride(NO328 hydrochloride) is a selective gamma-aminobutyric acid (GABA) reuptake inhibitor.Target: GABA reuptake inhibitorTiagabine had an early onset of effect, as shown by significant reduction from baseline in mean HAM-A total score compared with placebo at week 1 (observed cases, p < .05). Tiagabine was generally well tolerated and not associated with changes in sexual functioning or depressive status. Symptoms of a discontinuation syndrome during taper were not observed. Tiagabine may be a useful treatment option for adult patients diagnosed with GAD [1]. Tiagabine was generally well tolerated; the most common adverse events were nausea, dizziness and headaches [2]. Tiagabine (0.1 microM), an antiepileptic drug that specifically inhibits the GAT-1 GABA transporter inhibited GABA uptake 50% in temporal cortex and 60-68% in white structures [3].

  • CAS Number: 145821-59-6
  • MF: C20H26ClNO2S2
  • MW: 412.009
  • Catalog: GABA Receptor
  • Density: N/A
  • Boiling Point: 568ºC at 760 mmHg
  • Melting Point: >192oC dec.
  • Flash Point: 297.3ºC

Epi-galantamine

Epi-galantamine is a diastereomer of Galantamine. Epi-galantamine is an alkaloid isolated from the bulbs and flowers of Caucasian snowdrop (Galanthus woronowii). Epi-galantamine inhibits AChE with an EC50 of 45.7 μM[1][2][3].

  • CAS Number: 1668-85-5
  • MF: C17H21NO3
  • MW: 287.35400
  • Catalog: AChE
  • Density: 1.28g/cm3
  • Boiling Point: 439.3ºC at 760 mmHg
  • Melting Point: 183-185ºC
  • Flash Point: 219.5ºC

Harmane

Harmane, a β-Carboline alkaloid (BCA), is a potent neurotoxin that causes severe action tremors and psychiatric manifestations. Harmane shows 1000-fold selectivity for I1-Imidazoline receptor (IC50=30 nM) over α2-adrenoceptor (IC50=18 μM). Harmane is also a potent and selective inhibitor of monoamine oxidase (MAO) (IC50s=0.5 and 5 μM for human MAO A/B, respectively). Harmane exhibits comutagenic effect[1][2][3][4].

  • CAS Number: 486-84-0
  • MF: C12H10N2
  • MW: 182.221
  • Catalog: Adrenergic Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 386.9±22.0 °C at 760 mmHg
  • Melting Point: 235-238 °C(lit.)
  • Flash Point: 176.2±13.6 °C

M3 receptor antagonist 1

M3 receptor antagonist 1 is a muscarinic M3-receptor antagonist extracted from patent WO 2008012290 A2, formula Ic.

  • CAS Number: 1004312-94-0
  • MF: C27H25BrF4N2O3S
  • MW: 613.46
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

VU0152099

VU0152099 is a potent, selective, CNS-penetrant positive allosteric modulator of M4 mAChR with EC50 of 403 nM; shows no agonist activity but potentiates responses of M(4) to acetylcholine, and is devoid of activity at other mAChR subtypes or at a panel of other GPCRs; reverses amphetamine-induced hyperlocomotion in rats.

  • CAS Number: 612514-42-8
  • MF: C18H17N3O3S
  • MW: 355.411
  • Catalog: mAChR
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 622.9±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 330.5±31.5 °C

Nevadistinel

Nevadistinel (NYX-458; NYX-3054) is a positive allosteric modulator of N-methyl-D-aspartate (NMDA) receptor. Nevadistinel can be used to inhibit cognitive impairment associated with neurodegenerative diseases, such as mild cognitive impairment, mild Alzheimer's disease, Parkinson's disease, Lewy body disease[1].

  • CAS Number: 2181816-92-0
  • MF: C15H18N2O3
  • MW: 274.32
  • Catalog: iGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

H-D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (Disulfide bond between Cys2 and Pen7)

CTAP is a potent, highly selective, and brain penetrant μ opioid receptor antagonist (IC50=3.5 nM) and displays over 1200-fold selectivity over δ opioid (IC50=4500 nM) and somatostatin receptors. CTAP can be used for the study of L-DOPA-induced dyskinesia (LID)[1].

  • CAS Number: 103429-32-9
  • MF: C51H69N13O11S2
  • MW: 1104.304
  • Catalog: Opioid Receptor
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

LY2183240

LY2183240 is a novel and highly potent blocker of anandamide uptake (IC50 = 270 pM). LY2183240 inhibits fatty acid amide hydrolase (FAAH) activity (IC50 = 12.4 nM). IC50: 270 pM (anandamide uptake); 12.4 nM (FAAH)Target: FAAH; Anandamide uptakeFollowing i.p. administration in rats, LY2183240 increases brain anandamide concentration and exerts antinociceptive effects in formalin model of pain.

  • CAS Number: 874902-19-9
  • MF: C17H17N5O
  • MW: 307.350
  • Catalog: FAAH
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 506.1±53.0 °C at 760 mmHg
  • Melting Point: 87-88ºC
  • Flash Point: 259.9±30.9 °C

rac Fesoterodine-d14 Fumarate

(Rac)-Fesoterodine-d14 fumarate is a labelled racemic 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: 1185237-08-4
  • MF: C30H27D14NO7
  • MW: 541.73500
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ABT 724 trihydrochloride

ABT-724 trihydrochloride is a potent and highly selective dopamine D4 receptor agonist with an EC50 of 12.4 nM for human dopamine D4 receptor. ABT-724 trihydrochloride is a potent partial agonist at the rat D4 (EC50 of 14.3 nM) and the ferret D4 receptor (EC50 of 23.2 nM), and has no effect on dopamine D1, D2, D3, or D5 receptors. ABT-724 trihydrochloride could be useful for the treatment of erectile dysfunction and has favorable side-effect profile[1].

  • CAS Number: 587870-77-7
  • MF: C17H22Cl3N5
  • MW: 402.749
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AC260584

AC260584 is an M1 muscarinic receptor allosteric agonist with a pEC50 of 7.6.

  • CAS Number: 560083-42-3
  • MF: C20H29FN2O2
  • MW: 348.45500
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cisatracurium Besylate

Cisatracurium Besylate is a nondepolarizing neuromuscular blocking agent, antagonizing the action of acetylcholine by inhibiting neuromuscular transmission.Target: AChR alpha-2Cisatracurium is a neuromuscular-blocking drug or skeletal muscle relaxant in the category of non-depolarizing neuromuscular-blocking drugs, used adjunctively in anesthesia to facilitate endotracheal intubation and to provide skeletal muscle relaxation during surgery or mechanical ventilation. It is a bisbenzyltetrahydroisoquinolinium agent with an intermediate duration of action. Cisatracurium is one of the ten isomers of the parent molecule, atracurium. Moreover, cisatracurium represents approximately 15% of the atracurium mixture [1, 2].

  • CAS Number: 96946-42-8
  • MF: C65H82N2O18S2
  • MW: 1243.479
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 90-93ºC
  • Flash Point: N/A

Tramiprosate

Tramiprosate is a small, orally-administered compound that binds to soluble Aβ and reduces amyloid aggregation and subsequent depositiontarget: AβIn vitro: Tramiprosate provides neuroprotection against Aβ-induced neurotoxicity in neuronal and mouse organotypic hippocampal cultures, and reverses Aβ-induced long-term potentiation (LTP) inhibition in rat hippocampus, in part, through activation of β-aminobutyric acid A (GABA-A) receptors. Tramiprosate dose-dependently provides neuroprotection against ischemic stroke.In vivo: Tramiprosate produced dose-dependent reductions of Aβ in the brain of transgenic mice (hAPP-TgCRND8). Clinical studies show that tramiprosate was safe and tolerable. In mild-to-moderate AD patients tramiprosate also reduced Aβ42 levels in CSF.The reference for animal administration is 50 mg/kg.

  • CAS Number: 3687-18-1
  • MF: C3H9NO3S
  • MW: 139.173
  • Catalog: Amyloid-β
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: 293 °C (dec.)(lit.)
  • Flash Point: N/A

MAO-B-IN-1

MAO-B-IN-1 is an inhibitor of monoamine oxidase B, used for the research of neurological diseases.

  • CAS Number: 1124198-17-9
  • MF: C16H14F3N3O2S
  • MW: 369.36
  • Catalog: Monoamine Oxidase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Acetylisoeugenol

Isoeugenol acetate, an essential oil constituent of nutmeg, clove, and cinnamon, shows excellent inhibitory effects against some metabolic enzymes such as acetylcholinesterase (AChE) enzymes (IC50=77 nM; Ki=16 nM), α-glycosidase (IC50=19.25 nM; Ki=21 nM), and α-amylase (IC50=411.5 nM). Isoeugenol acetate is used medical and cosmetics industries for its antioxidant, anticancer, antimicrobial and anti-inflammatory properties[1][2].

  • CAS Number: 93-29-8
  • MF: C12H14O3
  • MW: 206.238
  • Catalog: AChE
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 283.0±20.0 °C at 760 mmHg
  • Melting Point: 79-81 °C(lit.)
  • Flash Point: 113.9±16.4 °C

mGAT3/4-IN-1

mGAT3/4-IN-1 (compound 19b) is a potent mGAT3/mGAT4 inhibitor, with pIC50 values of 5.31 and 5.24, respectively. mGAT3/4-IN-1 exhibits a significant tactile allodynia reduction in diabetic neuropathic mice[1].

  • CAS Number: 2556833-57-7
  • MF: C26H31ClN2O2S2
  • MW: 503.12
  • Catalog: GABA Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CY 208-243

CY 208-243 is a selective dopamine D1 receptor agonist which exhibits antiparkinsonian activity[1].

  • CAS Number: 100999-26-6
  • MF: C19H18N2
  • MW: 274.36000
  • Catalog: Dopamine Receptor
  • Density: 1.225 g/cm3
  • Boiling Point: 466.5ºC at 760 mmHg
  • Melting Point: 227-228ºC
  • Flash Point: 236ºC

Diethylaminoethyl

Aprophen (Aprofene) is an antimuscarinic inhibitor. Aprophen can be used for the research of central nervous system[1].

  • CAS Number: 3563-01-7
  • MF: C21H27NO2
  • MW: 325.44500
  • Catalog: mAChR
  • Density: 1.041g/cm3
  • Boiling Point: 434.8ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 132.5ºC

BMS-986163

BMS-986163 is a negative allosteric modulator of GluN2B. The prodrug BMS-986163 rapidly converts to its active parent molecule BMS-986169 (Ki=4 nM, IC50=24 nM).

  • CAS Number: 1801151-09-6
  • MF: C23H28FN2O5P
  • MW: 462.45
  • Catalog: iGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

FAUC-365

FAUC 365 is a highly dopamine D3 receptor-selective antagonist with Ki values of 0.5 nM, 340, 2600, and 3600 nM at D3, D4.4, D2short, and D2Long receptors, respectively. FAUC 365 can be used for the research of schizophrenia, and Parkinson's disease[1][2].

  • CAS Number: 474432-66-1
  • MF: C23H25Cl2N3OS
  • MW: 462.435
  • Catalog: Dopamine Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 680.3±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 365.2±31.5 °C

Procaine hydrochloride

Procaine Hydrochloride is a local anesthetic drug of the amino ester group.Target: OthersProcaine is a local anesthetic of the ester type that has a slow onset and a short duration of action.Procaine (0.01-100 microM) inhibited the 5-HT3 receptor-mediated inward current in the whole-cell patch clamp recording. Procaine appears to produce a competitive inhibition on 5-HT3 receptors with a KD of 1.7 microM [1]. Procaine is a DNA-demethylating agent that produces a 40% reduction in 5-methylcytosine DNA content as determined by high-performance capillary electrophoresis or total DNA enzyme digestion. Procaine can also demethylate densely hypermethylated CpG islands. Procaine also has growth-inhibitory effects in these cancer cells, causing mitotic arrest [2]. Procaine functions as an excitant of limbic system cells, and that procaine alters synaptic transmission in some, but not all, output pathways from the amygdale [3].

  • CAS Number: 51-05-8
  • MF: C13H21ClN2O2
  • MW: 272.771
  • Catalog: GABA Receptor
  • Density: N/A
  • Boiling Point: 195-196°C 17mm
  • Melting Point: 155-156 °C(lit.)
  • Flash Point: 195-196°C/17mm