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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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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ERK JNK KLF MAP3K MAP4K MAPKAPK2 (MK2) MEK Mixed Lineage Kinase MNK p38 MAPK Raf Ribosomal S6 Kinase (RSK)
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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
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Pargyline

Pargyline is an irreversible non-selective monoamine oxidase (MAO) inhibitor drug (IC50 for MAO-A is 11.52 nM and for MAO-B is 8.2 nM) .

  • CAS Number: 555-57-7
  • MF: C11H13N
  • MW: 159.22800
  • Catalog: Monoamine Oxidase
  • Density: 0.94
  • Boiling Point: 86-88ºC(4 torr)
  • Melting Point: 156 - 160ºC
  • Flash Point: 83ºC

TACA

TACA (trans-4-Aminocrotonic acid) is a potent agonist of GABAA and GABAC receptors (KD= 0.6 μM). TACA also is GABA uptake inhibitor and substrate for GABA-T. TACA produces late biphasic responses in the MPG neurons[1][2][3].

  • CAS Number: 38090-53-8
  • MF: C4H7NO2
  • MW: 101.10400
  • Catalog: GABA Receptor
  • Density: 1.169 g/cm3
  • Boiling Point: 300.4ºC at 760 mmHg
  • Melting Point: >158°C (lit.)
  • Flash Point: 135.5ºC

Tiotropium-d6 bromide

Tiotropium-d6 (bromide) is deuterium labeled Tiotropium (Bromide). Tiotropium Bromide (BA679 BR) is a muscarinic acetylcholine receptor (mAChR) antagonist that blocks the binding of the acetylcholine ligand and subsequent opening of the ligand-gated ion channel.

  • CAS Number: 1126775-44-7
  • MF: C19H16D6BrNO4S2
  • MW: 478.45
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GNE 0723

GNE 0723 is a brain permeable positive allosteric modulator of NMDAR, with an EC50 of 21 nM for GluN2A, 7.4 and 6.2 μM for GluN2C and GluN2D, respectively.

  • CAS Number: 1883518-31-7
  • MF: C16H8ClF6N5OS
  • MW: 467.776
  • Catalog: iGluR
  • Density: 1.8±0.1 g/cm3
  • Boiling Point: 505.2±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 259.4±32.9 °C

2614W94

2614W94 is a selective, reversible inhibitor of monoamine oxidase-A with a competitive mechanism of inhibition and IC50 of 5 nM and Ki of 1.6 nM with serotonin as substrate.

  • CAS Number: 205187-35-5
  • MF: C15H11F3O4S
  • MW: 344.306
  • Catalog: Monoamine Oxidase
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 440.8±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 220.4±28.7 °C

MM 77 dihydrochloride

MM 77 dihydrochloride is a potent postsynaptic antagonist of the 5-HT1A receptor. MM 77 dihydrochloride exhibits anxiolytic-like activity[1][2].

  • CAS Number: 159187-70-9
  • MF: C19H29Cl2N3O3
  • MW: 418.358
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ansofaxine hydrochloride

Ansofaxine hydrochloride (LY03005; LPM570065) is a triple reuptake inhibitor; inhibits serotonin, dopamine and norepinephrine reuptake with IC50 values of 723, 491 and 763 nM, respectively.

  • CAS Number: 916918-84-8
  • MF: C24H32ClNO3
  • MW: 417.97
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

L-Glutamic acid-13C5,15N

L-Glutamic acid-13C5,15N is the 13C- and 15N-labeled L-Glutamic acid. L-Glutamic acid acts as an excitatory transmitter and an agonist at all subtypes of glutamate receptors (metabotropic, kainate, NMDA, and AMPA). L-Glutamic acid shows a direct activating effect on the release of DA from dopaminergic terminals.

  • CAS Number: 202468-31-3
  • MF: 13C5H915NO4
  • MW: 153.09
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Herkinorin

Herkinorin is a potent and selective agonist of µ opioid receptor with a Ki of 45 nM Herkinorin is widely used for pain research[1].

  • CAS Number: 862073-77-6
  • MF: C28H30O8
  • MW: 494.53300
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

UNC9995

UNC9995 is a β-arrestin2-biased agonist of dopamine receptor Drd2. UNC9995 inhibits NLRP3 inflammasome activation by enhancing β-arrestin2-NLRP3 interaction, thus prevents neuronal degeneration. Futhermore, UNC9995 activates the Drd2/β-arrestin2 signaling to prevent inflammation-related genes transcription-induced by JAK/STAT3. UNC9995 improves depressive behavior in mouse model, and improves astrocytes dysfunctions[1].

  • CAS Number: 1354030-52-6
  • MF: C20H21Cl2N3OS
  • MW: 422.37
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Blonanserin dihydrochloride

Blonanserin dihydrochloride is a potent and orally active 5-HT2A and dopamine D2 receptor antagonist, with Ki values of 0.812 and 0.142 nM, respectively. Blonanserin dihydrochloride is usually acts as an atypical antipsychotic agent, and can be used for the research of extrapyramidal symptoms, excessive sedation, or hypotension[1][2].

  • CAS Number: 132812-45-4
  • MF: C23H32Cl2FN3
  • MW: 440.42
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Fenitrothion

Fenitrothion, one of the most widely used organophosphorus pesticides, is a cholinesterase inhibiting insecticide/acaricid. Fenitrothion is widely used, as a broad-spectrum insecticide, on cotton crops, vegetables crops, fruit crops, and field crops especially paddy. Fenitrothion leads to accumulation of nitrophenols[1][2].

  • CAS Number: 122-14-5
  • MF: C9H12NO5PS
  • MW: 277.234
  • Catalog: AChE
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 349.5±52.0 °C at 760 mmHg
  • Melting Point: 3.4°C
  • Flash Point: 165.2±30.7 °C

α-Conotoxin BuIA

α-Conotoxin BuIA is a paralytic peptide neurotoxin and a competitive nAChR antagonist, with IC50s of 0.258 nM (α6/α3β2), 1.54 nM (α6/α3β4), 5.72 nM (α3β2), respectively. α-Conotoxin BuIA can be used to distinguish nAChRs containing β2- and β4-subunit, respectively. α-Conotoxin BuIA distinguishes among αxβ2 nAChRs with a rank order potency of α6>α3>α2>α4[1].

  • CAS Number: 846539-62-6
  • MF: C54H82N14O16S4
  • MW: 1311.57
  • Catalog: nAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ginkgolide A

Ginkgolide A is an extract from in Ginkgo biloba and a g-aminobutyric acid (GABA) antagonist.Target: GABA ReceptorGinkgolide A is a highly active PAF antagonist cage molecule that is isolated from the leaves of the Ginkgo biloba tree. Shows potential in a wide variety of inflammatory and immunological disorders. Ginkgolide A significantly shortened the sleeping time induced by anesthetics in mice [1]. Ginkgolide A failed to affect apoptotic damage neither in serum-deprived nor in staurosporine-treated neurons [2].

  • CAS Number: 15291-75-5
  • MF: C20H24O9
  • MW: 408.399
  • Catalog: GABA Receptor
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 710.1±60.0 °C at 760 mmHg
  • Melting Point: 280°C (dec.)
  • Flash Point: 256.5±26.4 °C

5-HT2 agonist-1 free base

5-HT2 agonist-1 (Compound 24) free base is a 5-HT2A & 5-HT2B & 5-HT2C agonist, with IC50s of 10 nM, 8.3, and 1.6 nM respectively. 5-HT2 agonist-1 free base can be used for research of depression, alcoholism, tobacco and cocaine addiction, inflammation, cluster headache, PTSD, seizure disorders and other CNS disorders[1].

  • CAS Number: 2708279-77-8
  • MF: C19H22N2O2
  • MW: 310.39
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

3-Amino-4-phenylbutyric acid hydrochloride

Phenibut (β-Phenyl-GABA) hydrochloride is an orally active GABA-B agonist[1]. Phenibut hydrochloride acts as a GABA-mimetic, primarily at GABAB receptors. Phenibut hydrochloride has anxiolytic and nootropic (cognition enhancing) effects[2].

  • CAS Number: 3060-41-1
  • MF: C10H14ClNO2
  • MW: 215.677
  • Catalog: GABA Receptor
  • Density: 1.161g/cm3
  • Boiling Point: 327.8ºC at 760 mmHg
  • Melting Point: 194-201ºC
  • Flash Point: 152.1ºC

Alizapride

Alizapride is a potent antiemetic, acting as a dopamine receptor antagonist. Alizapride also used in human digestive disorders[1][3].

  • CAS Number: 59338-93-1
  • MF: C16H21N5O2
  • MW: 315.37000
  • Catalog: Dopamine Receptor
  • Density: 1.224 g/cm3
  • Boiling Point: 597.6ºC at 760 mmHg
  • Melting Point: 3360°C
  • Flash Point: 315.2ºC

Flumazenil

Flumazenil is a competitive GABAA receptor antagonist, used in the treatment of benzodiazepine overdoses.

  • CAS Number: 78755-81-4
  • MF: C15H14FN3O3
  • MW: 303.288
  • Catalog: GABA Receptor
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 528.0±50.0 °C at 760 mmHg
  • Melting Point: 201-203°C
  • Flash Point: 273.1±30.1 °C

BMS-986121

BMS-986121 is a positive allosteric modulator (PAM) of the μ opioid receptor extracted from patent WO2014107344. BMS-986121 is built on a chemical scaffold representing a new chemotype for μ receptor PAMs[1][2][3].

  • CAS Number: 313671-26-0
  • MF: C15H9Cl2N3O2S
  • MW: 366.22
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Methiothepin Maleate

Methiothepin maleate is a potent and non-selective 5-HT2 receptor antagonist, with pKds of 7.10 (5-HT1A), 7.28 (5HT1B), 7.56 (5HT1C), 6.99 (5HT1D), 7.0 (5-HT5A), 7.8 (5-HT5B), 8.74 (5-HT6), and 8.99 (5-HT7), and pKis of 8.50 (5HT2A), 8.68 (5HT2B), and 8.35 (5HT2C).

  • CAS Number: 19728-88-2
  • MF: C24H28N2O4S2
  • MW: 472.62
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: 462.9ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 233.8ºC

Bifemelane hydrochloride

Bifemelane hydrochloride is a potent, selective and competitive inhibitor of monoamine oxidase A (MAO-A), with a Ki of 4.20 μM, and it also inhibits MAO-B noncompetitively with a Ki of 46.0 μM. Bifemelane hydrochloride has a potent antidepressant activity and can be used for the research of cognitive and emotional disturbances related to cerebrovascular disease[1][2].

  • CAS Number: 62232-46-6
  • MF: C18H24ClNO
  • MW: 305.84200
  • Catalog: Monoamine Oxidase
  • Density: N/A
  • Boiling Point: 395.4ºC at 760 mmHg
  • Melting Point: 117-121°C
  • Flash Point: 169.2ºC

Mesembrine-d3

Mesembrine-d3 ((+)-Mesembrine-d3) is the deuterium labeled Mesembrine. Mesembrine ((+)-Mesembrine) a main alkaloid that features an aryloctahydroindole skeleton. Mesembrine is a 5-HT transporter inhibitor with a Ki of 1.4 nM. Mesembrine also inhibits phosphodiesterase 4B (PDE4B) with an IC50 of 7.8 μM[1][2].

  • CAS Number: 1346600-05-2
  • MF: C17H20D3NO3
  • MW: 292.39
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ro 25-6981 maleate

Ro 25-6981 Maleate is a potent and selective activity-dependent blocker of NMDA receptors containing the NR2B subunit. IC50 values are 0.009 and 52 μM for cloned receptor subunit combinations NR1C/NR2B and NR1C/NR2A respectively.IC50 value: 9 nM [1]Target: NMDA receptor subtype of NR1C & NR2Bin vitro: Ro 25-6981 inhibited 3H-MK-801 binding to rat forebrain membranes in a biphasic manner with IC50 values of 0.003 microM and 149 microM for high- (about 60%) and low-affinity sites, respectively. NMDA receptor subtypes expressed in Xenopus oocytes were blocked with IC50 values of 0.009 microM and 52 microM for the subunit combinations NR1C & NR2B and NR1C & NR2A, respectively, which indicated a >5000-fold selectivity [1]. Increasing the concentration of spermidine did not change the efficacy of RO 25-6981 and minimally changed the IC(50) value. Epsilon1Q336R receptors were more inhibited by ifenprodil and RO 25-9681 than wildtype epsilon1 receptors in ligand binding assays but not in functional assays [2].in vivo: Intrathecal injection of Ro 25-6981 significantly enhanced the paw withdrawal mechanical threshold and paw withdrawal thermal latency after the operation. Significant change has been observed after intrathecal injection of 800.0 μg of Ro 25-6981 and at 2h after operation in the oblique pull test degree and BBB rating score. Pretreatment of Ro 25-6981 decreased the high level expression of NR2B with tyrosine phosphorylation in spinal dorsal horn of the rat model after the operation [3].

  • CAS Number: 1312991-76-6
  • MF: C26H33NO6
  • MW: 455.543
  • Catalog: iGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

LY-411575 (isomer 1)

LY-411575 isomer 1 is an isomer of LY411575, which is a potent γ-secretase inhibitor.

  • CAS Number: 209984-58-7
  • MF: C26H23F2N3O4
  • MW: 479.47500
  • Catalog: γ-secretase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Selurampanel

Selurampanel (BGG 492) is an orally active and competitive AMPA receptor antagonist with an IC50 of 190 nM. Selurampanel has reasonable blood-brain barrier penetration. Selurampanel can be used for epilepsy research[1][2].

  • CAS Number: 912574-69-7
  • MF: C16H19N5O4S
  • MW: 377.42
  • Catalog: iGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(S)-Willardiine

(S)-Willardiine is a potent agonist of AMPA/kainate receptors with EC50 of 44.8 uM.IC50 value: 44.8 uM(EC50) [1]Target: AMPA/kainate receptor agonistin vitro: The (S)- but not (R)-isomers of willardiine and 5-bromowillardiine were potent agonists, producing rapidly but incompletely desensitizing responses [1]. At a concentration of 1.8 mM, Ca2+ inhibited the currents induced by 100 microM willardiine by approximately 50% [2].in vivo: In newborn mice (P5, histopathology at P10), local injection of the AMPA receptor agonist S-bromo-willardiine at day 5 after birth induced cortical damage and white matter damage, which was reduced in a dose-dependent manner by the AMPA receptor antagonists [3].

  • CAS Number: 21416-43-3
  • MF: C7H9N3O4
  • MW: 199.16400
  • Catalog: iGluR
  • Density: 1.501 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NH 125

NH125 is a potent and selective inhibitor of eukaryotic elongation factor 2 kinase (eEF-2K/CaMKIII), also could induce eEF2 phosphorylation, with an IC50 of 60 nM for eEF-2K.

  • CAS Number: 278603-08-0
  • MF: C27H45IN2
  • MW: 524.564
  • Catalog: CaMK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 88.2-94.9ºC
  • Flash Point: N/A

13-Hydroxyisobakuchiol

Hydroxyisobakuchiol (Delta3,2-Hydroxylbakuchiol), an analog of Bakuchiol (HY-N0235) isolated from Psoralea corylifolia (L.), is a potent monoamine transporter inhibitor. 13-Hydroxyisobakuchiol is more selective for the dopamine transporter (DAT) (IC50=0.58 μM) and norepinephrine transporter (NET) (IC50=0.69 μM) than for the serotonin transporter (SERT) (IC50=312.02 μM). 13-Hydroxyisobakuchiol has the potential for the research of disorders such as Parkinson's disease, depression, and cocaine addiction[1].

  • CAS Number: 178765-49-6
  • MF: C18H24O2
  • MW: 272.382
  • Catalog: Monoamine Transporter
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 429.3±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 195.8±23.3 °C

BuChE-IN-6

BuChE-IN-6 (compound 1b) is a potent and selective BuChE (butyrylcholinesterase) inhibitor, with IC50 values of 0.46 and 0.51 μM for eqBuChE and hBuChE, respectively. BuChE-IN-6 also inhibits Aβ42 self-aggregation[1].

  • CAS Number: 2003213-07-6
  • MF: C21H26N4O2
  • MW: 366.46
  • Catalog: AChE
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(±)-Marmesin

(±)-Marmesin is a good precursor of the linear furanocoumarins. (±)-Marmesin derivatives have high degree of acetylcholinesterase inhibitory property[1][2].

  • CAS Number: 13710-70-8
  • MF: C14H14O4
  • MW: 246.259
  • Catalog: AChE
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 434.0±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 168.0±22.2 °C