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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SB 205607 dihydrobromide

A potent and selective δ-opioid receptor agonist that has high affinity and selectivity for the δ1 subtype with Ki of 1.12 nM; dispalys >1,000-fold selectivity over μOR and κOR; Pain Discontinued

  • CAS Number: 1217628-73-3
  • MF: C23H24N2O.2HBr
  • MW: 506.273
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

5-bromo-N-(2-morpholinoethyl)nicotinamide

WAY-620147 (compound 6) is an N-(2-morpholinoethyl)nicotinamide derivative that inhibits monoamine oxidase (Monoamine Oxidase). WAY-620147 inhibits MAO-A and MAO-B with IC50s of 26 μM and 55 μM, respectively[1].

  • CAS Number: 515866-67-8
  • MF: C12H16BrN3O2
  • MW: 314.178
  • Catalog: Monoamine Oxidase
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 465.4±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 235.3±28.7 °C

Isopteropodine

Isopteropodine is heteroyohimbine-type oxindole alkaloid components of Uncaria tomentosa (Willd.) DC. Isopteropodine acts as positive modulators of muscarinic M1 and 5-HT2 receptors[1].

  • CAS Number: 5171-37-9
  • MF: C21H24N2O4
  • MW: 368.42600
  • Catalog: 5-HT Receptor
  • Density: 1.33g/cm3
  • Boiling Point: 555.2ºC at 760 mmHg
  • Melting Point: 209-211 °C
  • Flash Point: 289.6ºC

hMAO-B-IN-4

hMAO-B-IN-4 (compound B10) is a selective, reversible and blood–brain barrier (BBB) penetrable human monoamine oxidase-B (hMAO-B) inhibitor with an IC50 value and a Ki value of 0.067 and 0.03 μM, respectively. hMAO-B-IN-4 inhibits hMAO-A with an IC50 value of 33.82 μM. hMAO-B-IN-4 can be used for Alzheimer’s disease (AD) and Parkinson’s disease (PD) research[1].

  • CAS Number: 1666119-75-0
  • MF: C20H16O2S
  • MW: 320.40
  • Catalog: Monoamine Oxidase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Fluoroethylnormemantine hydrochloride

Fluoroethylnormemantine hydrochloride, a derivative of Memantine, is an antagonist of the N-methyl-D-aspartate (NMDA) receptor. [18F]-Fluoroethylnormemantine hydrochloride can be used as a positron emission tomography (PET) tracer. Fluoroethylnormemantine hydrochloride exhibits anti-amnesic, neuroprotective, antidepressant-like and fear-attenuating effects[1][2][3].

  • CAS Number: 1639210-25-5
  • MF: C12H21ClFN
  • MW: 233.75
  • Catalog: iGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CP 93129 dihydrochloride

CP 93129 dihydrochloride is a potent 5HT1B receptor agonist. CP 93129 dihydrochloride has the potential for parkinson's disease research[1].

  • CAS Number: 879089-64-2
  • MF: C12H15Cl2N3O
  • MW: 288.17300
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Nalfurafine

Nalfurafine (TRK-820) is a potent selective and orally active G protein-biased kappa opioid receptor (KOR)-agonist with high translational potential[1]. Nalfurafine (TRK-820) enhances the therapeutic potential of MOR-targeting analgesics, has the potential for uremic pruritis treatment[2].

  • CAS Number: 152657-84-6
  • MF: C28H32N2O5
  • MW: 476.56400
  • Catalog: Opioid Receptor
  • Density: 1.41g/cm3
  • Boiling Point: 700.7ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 377.6ºC

AZD7325

AZD7325 is a potent and orally active partial selective PAM of GABAAα2 and Aα3 receptor (Ki=0.3 and 1.3 nM, respectively), and has less antagonistic efficacy at the Aα1 and Aα5 receptor subtypes[1][4]. AZD7325 is a moderate CYP1A2 and a potent CYP3A4 inducer in vitro[2]. AZD7325 has the potential for the investigation of anxiety and dravet syndrome[3]. PAM: positive allosteric modulator.

  • CAS Number: 942437-37-8
  • MF: C19H19FN4O2
  • MW: 354.378
  • Catalog: GABA Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GR 94800 TFA

GR 94800 is a potent and selective NK2 receptor peptide antagonist, with pKB values of 9.6, 6.4 and 6.0 for NK2, NK1 and NK3 receptors, respectively[1][2].

  • CAS Number: 141636-65-9
  • MF: C49H61N9O8
  • MW: 904.06400
  • Catalog: Neurokinin Receptor
  • Density: 1.282 g/cm3
  • Boiling Point: 1310.4ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 746.3ºC

SNC 162

SNC162 is a delta-opioid receptor agonist with an IC50 of 0.94 nM. SNC162 has antidepressant-like effects and produces a selective enhancement of the antinociceptive effects of fentanyl in rhesus monkeys[1][2].

  • CAS Number: 178803-51-5
  • MF: C27H37N3O
  • MW: 419.60
  • Catalog: Opioid Receptor
  • Density: 1.027g/cm3
  • Boiling Point: 536.4ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 202.4ºC

(RS)-AMPA

(RS)-AMPA ((±)-AMPA) is a glutamate analogue and a potent and selective excitatory neurotransmitter L-glutamic acid agonist. (RS)-AMPA does not interfere with binding sites for kainic acid or NMDA receptors[1][2].

  • CAS Number: 77521-29-0
  • 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: 240ºC
  • Flash Point: 211.2±28.7 °C

Darifenacin-d4

Darifenacin-d4 is the deuterium labeled Darifenacin[1]. Darifenacin(UK88525) is a selective M3 muscarinic receptor antagonist with pKi of 8.9. IC50 value: 8.9 (pKi)[2].

  • CAS Number: 1095598-84-7
  • MF: C28H26D4N2O2
  • MW: 430.57
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Zuclopenthixol

Zuclopenthixol is a thioxanthene derivative which acts as a mixed dopamine D1/D2 receptor antagonist.

  • CAS Number: 53772-83-1
  • MF: C22H25ClN2OS
  • MW: 400.96500
  • Catalog: Dopamine Receptor
  • Density: 1.289g/cm3
  • Boiling Point: 577.4ºC at 760mmHg
  • Melting Point: 56-60ºC
  • Flash Point: 303ºC

LY 344864

LY344864 is a selective receptor agonist with an affinity of 6 nM (Ki) at the recently cloned 5-HT1F receptor.IC50 Value: 6 nM (Ki) [1]Target: 5-HT1FLY344864 possesses little affinity for the 56 other serotonergic and non-serotonergic neuronal binding sites examined [1].in vitro: he 5-HT1A, 5-HT1B and 5-HT1D receptor agonists 8-OH-DPAT (3 microM), CP93129 (3 microM) and L694247 (3 microM), but not the 5-HT1F receptor agonist LY344864 (1 - 3 microM) inhibited evoked IPSCs [2].in vivo: After an intravenous dose of 1 mg/kg, rat plasma LY344864 levels declined with time whereas brain cortex levels remained relatively constant for the first 6 hours after injection. Oral and intravenous LY344864 administration potently inhibited dural protein extravasation caused by electrical stimulation of the trigeminal ganglion in rats [1]. Sumatriptan, zolmitriptan, rizatriptan, and naratriptan all contracted the rabbit saphenous vein from baseline tone, whereas LY344864 in concentrations up to 10(-4) M did not contract the rabbit saphenous vein. Furthermore, vascular contractions to sumatriptan were markedly augmented in the presence of prostaglandin F(2alpha) (PGF(2alpha)). However, even in the presence of PGF(2alpha) (3 x 10(-7) M), LY344864 did not contract the rabbit saphenous vein in concentrations well in excess of its 5-HT(1F) receptor affinity (pK(i) = 8.2) [3].

  • CAS Number: 186544-26-3
  • MF: C21H22FN3O
  • MW: 351.417
  • Catalog: 5-HT Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 471.9±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 239.2±28.7 °C

haloperidol

Haloperidol is a potent dopamine D2 receptor antagonist, widely used as an antipsychotic.

  • CAS Number: 52-86-8
  • MF: C21H23ClFNO2
  • MW: 375.864
  • Catalog: Dopamine Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 529.0±50.0 °C at 760 mmHg
  • Melting Point: 152 °C
  • Flash Point: 273.8±30.1 °C

(+/-)-2-HYDROXYTRIDECANOICACID

(RS)-CPP ((±)-CPP) is a potent and selective NMDA antagonist. (RS)-CPP inhibits central neuron responses, and has anticonvulsant activity[1].

  • CAS Number: 100828-16-8
  • MF: C8H17N2O5P
  • MW: 252.20
  • Catalog: iGluR
  • Density: 1.408g/cm3
  • Boiling Point: 546.7ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 284.4ºC

JNJ-56022486

A novel potent and selective negative modulator of AMPA receptors containing TARP-gamma8

  • CAS Number: 2036082-79-6
  • MF: C15H10ClN3O
  • MW: 283.72
  • Catalog: iGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

hBChE-IN-2

hBChE-IN-2 (compound 15d) is a butyrylcholinesterase (BChE) inhibitor (IC50 of 0.62 μM) and a cannabinoid receptor 2 (CB2R) agonist. hBChE-IN-2 has neuroprotection activities[1].

  • CAS Number: 2923366-36-1
  • MF: C27H36N4O3
  • MW: 464.60
  • Catalog: Cannabinoid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Neurokinin B trifluoroacetate salt

Neurokinin B belongs to the tachykinin family of peptides. Neurokinin B binds a family of GPCRs—including neurokinin receptor 1 (NK1R), NK2R, and NK3R-to mediate their biological effect.

  • CAS Number: 86933-75-7
  • MF: C55H79N13O14S2
  • MW: 1210.42000
  • Catalog: Peptides
  • Density: 1.313 g/cm3
  • Boiling Point: 1646ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 949.3ºC

LY 344864 S-enantiomer

LY 344864 S-enantiomer is the S-enantiomer of LY344864. LY344864 is a 5-HT1F receptor agonist.

  • CAS Number: 186544-27-4
  • MF: C21H22FN3O
  • MW: 351.417
  • Catalog: 5-HT Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 471.9±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 239.2±28.7 °C

S-(+)-Mecamylamine hydrochloride

S-(+)-Mecamylamine (hydrochloride) is a neuronal nicotinic receptor modulator with antidepressant activity.

  • CAS Number: 107596-30-5
  • MF: C11H22ClN
  • MW: 203.75200
  • Catalog: nAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Lasmiditan hydrochloride

Lasmiditan hydrochloride is a high-affinity, highly selective 5-HT1F receptor agonist (Ki=2.1 nM), compared with Ki of 1043 nM and 1357 nM at the 5-HT(1B) and 5-HT(1D) receptors, respectively.IC50 value: 2.1 nM (Ki, 5-HT1F); >1000 nM (Ki, 5-HT1B/5-HT1D) [1]Target: 5-HT1F receptorin vitro: In vitro binding studies Lasmiditan showed a K(i) value of 2.21 nM at the 5-HT(1F) receptor, compared with K(i) values of 1043 nM and 1357 nM at the 5-HT(1B) and 5-HT(1D) receptors, respectively, a selectivity ratio greater than 470-fold. Lasmiditan show higher selectivity for the 5-HT(1F) receptor relative to other 5-HT(1) receptor subtypes than the first generation 5-HT(1F) receptor agonist LY334370. Unlike the 5-HT(1B/1D) receptor agonist sumatriptan, lasmiditan did not contract rabbit saphenous vein rings, a surrogate assay for human coronary artery constriction, at concentrations up to 100 μM.in vivo: In two rodent models of migraine, oral administration of lasmiditan potently inhibited markers associated with electrical stimulation of the trigeminal ganglion (dural plasma protein extravasation, and induction of the immediate early gene c-Fos in the trigeminal nucleus caudalis).

  • CAS Number: 613677-28-4
  • MF: C19H19ClF3N3O2
  • MW: 413.82
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Deoxyneocryptotanshinone

Deoxyneocryptotanshinone, a natural tanshinone, is a high affinity BACE1 (Beta-secretase) inhibitor with an IC50 value of 11.53 μM. Deoxyneocryptotanshinone shows a promising dose-dependent inhibition of protein tyrosine phosphatase 1B (PTP1B) with an IC50 value of 133.5 μM. Deoxyneocryptotanshinone can be used for Alzheimer's disease research[1][2].

  • CAS Number: 27468-20-8
  • MF: C19H22O3
  • MW: 298.376
  • Catalog: Phosphatase
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 468.0±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 251.0±25.2 °C

Batefenterol

Batefenterol (GSK961081;TD-5959) is a novel muscarinic receptor antagonist and β2-adrenoceptor agonist; displays high affinity for hM2, hM3 muscarinic and hβ2-adrenoceptor with Ki values of 1.4, 1.3 and 3.7 nM, respectively.

  • CAS Number: 743461-65-6
  • MF: C40H42ClN5O7
  • MW: 740.244
  • Catalog: Adrenergic Receptor
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 948.3±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 527.3±34.3 °C

Pilocarpine

Pilocarpine is a selective M3-type muscarinic acetylcholine receptor (M3 muscarinic receptor) agonist.

  • CAS Number: 92-13-7
  • MF: C11H16N2O2
  • MW: 208.257
  • Catalog: AMPK
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 431.8±18.0 °C at 760 mmHg
  • Melting Point: 34℃
  • Flash Point: 215.0±21.2 °C

Brasofensine sulfate

Brasofensine (BMS-204756) sulfate is a dopamine transporter antagonist and can be used for parkinson’s disease research[1].

  • CAS Number: 171655-92-8
  • MF: C16H22Cl2N2O5S
  • MW: 425.32700
  • Catalog: Monoamine Oxidase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

H-D-Glu(Gly-OH)-OH

gamma-DGG is a competitive AMPA receptor blocker.

  • CAS Number: 6729-55-1
  • MF: C7H12N2O5
  • MW: 204.18100
  • Catalog: iGluR
  • Density: N/A
  • Boiling Point: 586.6ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 308.6ºC

MK-3207 HCl

MK-3207 (Hydrochloride) is a potent and orally bioavailable CGRP receptor antagonist with IC50 of 0.12 nM and Ki of 0.024 nM, and is highly selective versus human AM1, AM2, CTR, and AMY3.

  • CAS Number: 957116-20-0
  • MF: C31H30ClF2N5O3
  • MW: 594.051
  • Catalog: CGRP Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

5-Hydroxyferulic acid

5-Hydroxyferulic acid is a hydroxycinnamic acid and is a metabolite of the phenylpropanoid pathway. 5-Hydroxyferulic acid is a precursor in the biosynthesis of sinapic acid and is also a COMT non-esterifed substrate[1][2][3].

  • CAS Number: 1782-55-4
  • MF: C10H10O5
  • MW: 210.18300
  • Catalog: COMT
  • Density: 1.44g/cm3
  • Boiling Point: 449.1ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 182.8ºC

Ocaperidone

Ocaperidone is an effective antipsychotic agent, acting as a potent 5-HT2 and dopamine D2 antagonist, and a 5-HT1A agonist, with Kis of 0.14 nM, 0.46 nM, 0.75 nM, 1.6 nM and 5.4 nM for 5-HT2, a1-adrenergic receptor, dopamine D2, histamine H1 and a2-adrenergic receptor, respectively, and a pEC50 and pKi of 7.60 and 8.08 for h5-HT1A.

  • CAS Number: 129029-23-8
  • MF: C24H25FN4O2
  • MW: 420.47900
  • Catalog: 5-HT Receptor
  • Density: 1.34g/cm3
  • Boiling Point: 588ºC at 760mmHg
  • Melting Point: 180-184°C
  • Flash Point: 309.4ºC