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 >
Arenavirus Bacterial CMV Enterovirus Filovirus Fungal HBV HCV HIV HSV Influenza Virus Parasite Reverse Transcriptase RSV SARS-CoV
Antibody-drug Conjugate >
ADC Cytotoxin ADC Linker Drug-Linker Conjugates for ADC PROTAC-linker Conjugate for PAC
Apoptosis >
Apoptosis Bcl-2 Family c-Myc Caspase DAPK Ferroptosis IAP MDM-2/p53 PKD RIP kinase Survivin Thymidylate Synthase TNF Receptor
Autophagy >
Autophagy LRRK2 ULK Mitophagy
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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
Cytoskeleton >
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Epigenetics >
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GPCR/G Protein >
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JAK/STAT Signaling >
EGFR JAK Pim STAT
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
PI3K/Akt/mTOR >
Akt AMPK ATM/ATR DNA-PK GSK-3 MELK mTOR PDK-1 PI3K PI4K PIKfyve PTEN
PROTAC >
PROTAC E3 Ligase Ligand-Linker Conjugate Ligand for E3 Ligase PROTAC Linker PROTAC-linker Conjugate for PAC
Protein Tyrosine Kinase/RTK >
Ack1 ALK Bcr-Abl BMX Kinase Btk c-Fms c-Kit c-Met/HGFR Discoidin Domain Receptor DYRK EGFR Ephrin Receptor FAK FGFR FLT3 IGF-1R Insulin Receptor IRAK Itk PDGFR PKA Pyk2 ROS Src Syk TAM Receptor Trk Receptor VEGFR
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Casein Kinase ERK Gli GSK-3 Hedgehog Hippo (MST) JAK Notch Oct3/4 PKA Porcupine ROCK sFRP-1 Smo STAT TGF-beta/Smad Wnt YAP β-catenin γ-secretase
TGF-beta/Smad >
TGF-beta/Smad PKC ROCK TGF-β Receptor
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VD/VDR
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Anisodamine

Racanisodamine is one of the racemic isomers of anisodamine, resembles anisodamine in pharmacological effect. Racanisodamine is a non-selective muscarinic antagonist, used as a component of eye drops for myopic control[1].

  • CAS Number: 17659-49-3
  • MF: C17H23NO4
  • MW: 305.369
  • Catalog: mAChR
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 474.6±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 240.8±28.7 °C

Brexpiprazole D8

Brexpiprazole D8 (OPC-34712 D8) is a deuterium labeled Brexpiprazole (OPC-34712). Brexpiprazole, an atypical antipsychotic drug, is a partial agonist of human 5-HT1A and dopamine receptor (Ki=0.12 nM and 0.3 nM, respectively). Brexpiprazole is also a 5-HT2A receptor antagonist (Ki=0.47 nM)[1][2].

  • CAS Number: 1427049-21-5
  • MF: C25H19D8N3O2S
  • MW: 441.615
  • Catalog: 5-HT Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 675.2±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 362.1±31.5 °C

CNS-5161,N'-(2-CHLORO-5-METHYLSULFANYL-PHENYL)-N-METHYL-N-(3-METHYLSULFANYL-PHENYL)-GUANIDINE

CNS-5161 is a novel NMDA ion-channel antagonist that interacts with the NMDA receptor/ion channel site to produce a noncompetitive blockade of the actions of glutamate.

  • CAS Number: 160754-76-7
  • MF: C16H18ClN3S2
  • MW: 351.92
  • Catalog: iGluR
  • Density: 1.25g/cm3
  • Boiling Point: 529.2ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 273.8ºC

Memantine-d3 hydrochloride

Memantine-d3 (hydrochloride) is deuterium labeled Memantine. Memantine is an orally active, noncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonist. Memantine can be used for the research of moderate-to-severe Alzheimer's disease (AD)[1][2][3].

  • CAS Number: 1329802-06-3
  • MF: C12H19D3ClN
  • MW: 218.78
  • Catalog: iGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Procyclidine hydrochloride

Procyclidine hydrochloride is a potent anti-cholinergic agent, and is also known to have NMDA antagonist properties.

  • CAS Number: 1508-76-5
  • MF: C19H30ClNO
  • MW: 323.90100
  • Catalog: iGluR
  • Density: N/A
  • Boiling Point: 433.5ºC at 760 mmHg
  • Melting Point: 85.5 to 86.5ºC
  • Flash Point: 205.7ºC

Veralipride

Veralipride is a D2 receptor antagonist. It is an alternative antidopaminergic treatment for menopausal symptoms.

  • CAS Number: 66644-81-3
  • MF: C17H25N3O5S
  • MW: 383.46300
  • Catalog: Dopamine Receptor
  • Density: 1.23 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Serotonin hydrochloride

Serotonin hydrochloride is a monoamine neurotransmitter in the CNS and an endogenous 5-HT receptor agonist. Serotonin hydrochloride is also a catechol O-methyltransferase (COMT) inhibitor with a Ki of 44 μM.

  • CAS Number: 153-98-0
  • MF: C10H13ClN2O
  • MW: 212.676
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: 416.1ºC at 760 mmHg
  • Melting Point: 149-154 °C(lit.)
  • Flash Point: 205.4ºC

DNQX

DNQX is a AMPA receptor antagonists.target: AMPA receptorIn vitro: DNQX, added 2 h after cell plating, induces a dose-dependent neurotoxicity.

  • CAS Number: 2379-57-9
  • MF: C8H4N4O6
  • MW: 252.141
  • Catalog: iGluR
  • Density: 1.7±0.1 g/cm3
  • Boiling Point: 670.7ºC at 760 mmHg
  • Melting Point: >300°C
  • Flash Point: 359.4ºC

Glycine-d5

Glycine-d5 is the deuterium labeled Glycine. Glycine is an inhibitory neurotransmitter in the CNS and also acts as a co-agonist along with glutamate, facilitating an excitatory potential at the glutaminergic N-methyl-D-aspartic acid (NMDA) receptors.

  • CAS Number: 4896-77-9
  • MF: C2D5NO2
  • MW: 80.097
  • Catalog: iGluR
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 240.9±23.0 °C at 760 mmHg
  • Melting Point: 240ºC (dec.)(lit.)
  • Flash Point: 99.5±22.6 °C

Darenzepine

Darenzepine is a muscarinic receptor inhibitor extracted from patent US 20170095465 A1.

  • CAS Number: 84629-61-8
  • MF: C21H21N3O2
  • MW: 347.41000
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MG 624

MG624 is a potent and selective neuronal α7 nAChR antagonist with a Ki of 106 nM[1].

  • CAS Number: 77257-42-2
  • MF: C22H30NO+
  • MW: 324.48000
  • Catalog: nAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CAY10499

MAGL-IN-5 is a non-selective lipase inhibitor with IC50 values of 144, 90, and 14 nM for human recombinant monoacylglycerol lipase(MAGL),hormone sensitive lipase(HSL), and fatty acid amide hydrolase(FAAH) respectively[1][2].

  • CAS Number: 359714-55-9
  • MF: C18H17N3O5
  • MW: 355.345
  • Catalog: FAAH
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SB-1436

SB-1436 is an Cholinesterase (ChE) inhibitor, inhibits acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and recombinant human acetylcholinesterase (rHuAChE) with IC50s of 0.176, 0.37 and 0.08 μM, respectively. SB-1436 inhibits AChE and BChE in a non-competitive manner with Kis of 0.046 and 0.115 μM, respectively. SB-1436 significantly stops the self-aggregation of Aβ, and can be used for neurological disease research[1].

  • CAS Number: 2925298-08-2
  • MF: C25H21ClFNO
  • MW: 405.89
  • Catalog: AChE
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

3-chloro-N-(pyridin-3-ylmethyl)-1-benzothiophene-2-carboxamide

GluR6 antagonist-1 is a benzothiophene derivative, acting as a GluR6 antagonist. GluR6 antagonist-1 can be used for researching acute and chronic neurological disorders[1].

  • CAS Number: 323176-64-3
  • MF: C15H11ClN2OS
  • MW: 302.779
  • Catalog: iGluR
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 543.5±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 282.5±30.1 °C

Cycrimine

Cycrimine is an orally active muscarinic cholinergic receptor (mAChR) M1 antagonist, reduces the acetylcholine levels in parkinson model. Cycrimine shows antispasmodic activity, can be used in studies of behavioral and mental disorder[1][2][3][4].

  • CAS Number: 77-39-4
  • MF: C19H29NO
  • MW: 287.44000
  • Catalog: mAChR
  • Density: 1.057g/cm3
  • Boiling Point: 433.5ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 205.7ºC

BACE2-IN-1

BACE2-IN-1 (compound 3l) is a highly selective BACE2 inhibitor with a Ki value of 1.6 nM. BACE2 inhibitors can be used to research of Type 2 Diabetes[1].

  • CAS Number: 1676107-08-6
  • MF: C36H38F3N3O3
  • MW: 617.70
  • Catalog: Beta-secretase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Facinicline hydrochloride

Facinicline hydrochloride (RG3487 hydrochloride) is an orally active nicotinic α7 receptor partial agonist, with a Ki of 6 nM for α7 human nAChR. Facinicline hydrochloride (RG3487 hydrochloride) improves cognition and sensorimotor gating in rodents. Facinicline hydrochloride (RG3487 hydrochloride) shows high affinity (antagonist) to 5-HT3Rs with a Ki value of 1.2 nM[1].

  • CAS Number: 677305-02-1
  • MF: C15H19ClN4O
  • MW: 306.79
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CP-809101

CP-809101 is a potent and selective 5-HT2C receptor agonist with pEC50 of 9.96/7.19/6.81 for human 5-HT2C/5-HT2B/5-HT2A receptors respectively. IC50 Value: 9.96(pEC50 for 5-HT2C); 7.19(pEC50 for 5-HT2B); 6.81(pEC50 for 5-HT2A)Target: 5-HT2C ReceptorCP-809101 is a potent, functionally selective 5-HT2C agonist that displays approximately 100% efficacy in vitro. The aim of the present studies was to assess the efficacy of a selective 5-HT2C agonist in animal models predictive of antipsychotic-like efficacy and side-effect liability. Similar to currently available antipsychotic drugs, CP-809101 dose-dependently inhibited conditioned avoidance responding (CAR, ED50 = 4.8 mg/kg, sc). CP-809101 antagonized both PCP- and d-amphetamine-induced hyperactivity with ED50 values of 2.4 and 2.9 mg/kg (sc), respectively and also reversed an apomorphine induced-deficit in prepulse inhibition. At doses up to 56 mg/kg, CP-809101 did not produce catalepsy. Thus, the present results demonstrate that the 5-HT2C agonist, CP-809101, has a pharmacological profile similar to that of the atypical antipsychotics with low extrapyramidal symptom liability. CP-809101 was inactive in two animal models of antidepressant-like activity, the forced swim test and learned helplessness.

  • CAS Number: 479683-64-2
  • MF: C15H17ClN4O
  • MW: 304.77
  • Catalog: 5-HT Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 486.6±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 248.1±28.7 °C

PF-04958242

PF-04958242 is a novel potent, selctive, and orally-active AMPA receptor (AMPAR) positive allosteric modulator (PAM) with Ki of 170 nM, EC50 of 370 nM; is under development for the treatment of cognitive symptoms in schizophrenia. Schizophrenia Phase 1 Discontinued

  • CAS Number: 1258963-59-5
  • MF: C18H20N2O4S2
  • MW: 381.509
  • Catalog: iGluR
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 531.0±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 275.0±32.9 °C

Paroxetine-d4 hydrochloride

Paroxetine-d4 (hydrochloride) is deuterium labeled Paroxetine (hydrochloride). Paroxetine hydrochloride is a potent selective serotonin-reuptake inhibitor, commonly prescribed as an and has GRK2 inhibitory ability with IC50 of 14 μM. Paroxetine hydrochloride can be used for the research of depressive disorder[1][2][3].

  • CAS Number: 2714485-95-5
  • MF: C19H17D4ClFNO3
  • MW: 369.85
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Isocorynoxeine

Isocorynoxeine, an isorhynchophylline-related alkaloid, exhibits a dose-dependent inhibition of 5-HT2A receptor-mediated current response with an IC50 of 72.4 μM.

  • CAS Number: 51014-29-0
  • MF: C22H26N2O4
  • MW: 382.453
  • Catalog: 5-HT Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 562.7±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 294.1±30.1 °C

MK-8931 TFA

Verubecestat (MK-8931) TFA is an orally active, high-affinity BACE1 and BACE2 inhibitor with Ki values of 2.2 nM and 0.38 nM. Verubecestat TFA effectively reduces Aβ40 and has the potential for Alzheimer's Disease[1][2].

  • CAS Number: 2095432-65-6
  • MF: C19H18F5N5O5S
  • MW: 523.43
  • Catalog: Beta-secretase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

U-101017

U-101017 is a partial agonist of benzodiazepine receptor and GABAA receptor, with anxiolytic effects. 

  • CAS Number: 170568-47-5
  • MF: C23H27ClN4O3
  • MW: 442.93800
  • Catalog: GABA Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CaMKII inhibitory peptide KIIN

CaMKII inhibitory peptide KIIN is a potent inhibitor of CaMKII[1][2].

  • CAS Number: 508181-45-1
  • MF: C136H240N44O39
  • MW: 3115.63
  • Catalog: CaMK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Trospium Chloride

Trospium Chloride is a competitive muscarinic cholinergic receptor antagonist.Target: mAChRTrospium chloride is an antimuscarinic agent indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency. Trospium has pharmacologic properties that are distinct from other antimuscarinic agents [1]. After oral administration, absorption of the hydrophilic trospium chloride is slow and incomplete. Peak plasma concentrations (Cmax) of approximately 4 ng/mL are reached 4-5 hours after administration of a 20 mg immediate-release preparation. The mean bioavailability is approximately 10% and decreases by concomitant food intake (to a mean of 26% of the fasting area under the plasma concentration-time curve [AUC]). Trospium chloride displays dose proportional increases in AUC and Cmax after a single dose within the clinically relevant dose range (20-60 mg). The mean volume of distribution is approximately 350-800 L [2].

  • CAS Number: 10405-02-4
  • MF: C25H30ClNO3
  • MW: 392.510
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 266-268ºC
  • Flash Point: N/A

(N,N,O-2H3)Glycine

Glycine-d3 is the deuterium labeled Glycine. Glycine is an inhibitory neurotransmitter in the CNS and also acts as a co-agonist along with glutamate, facilitating an excitatory potential at the glutaminergic N-methyl-D-aspartic acid (NMDA) receptors.

  • CAS Number: 4896-76-8
  • MF: C2H2D3NO2
  • MW: 78.09
  • Catalog: iGluR
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 240.9±23.0 °C at 760 mmHg
  • Melting Point: 240ºC (dec.)(lit.)
  • Flash Point: 99.5±22.6 °C

(R)-Dinotefuran

(R)-Dinotefuran ((R)-MTI-446), a neonicotinoid pesticide, exhibits comparative insecticidal activities (1.7-2.4 times) to typical sucking pests Aphis gossypii and Apolygus lucorum compared to racemic mixtures by inhibiting nicotinic acetylcholine receptors. (R)-Dinotefuran has a good efficacy in controlling target pests while minimizing hazard to honeybees[1].

  • CAS Number: 406466-53-3
  • MF: C7H14N4O3
  • MW: 202.21
  • Catalog: nAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

OM99-2 TFA

OM99-2 TFA, an eight residue peptidomimetic, tight-binding inhibitor of human brain memapsin 2 with a Ki value of 9.58 nM[1]. OM99-2 TFA is significantly advanced the development of BACE1 inhibitor[2], has the potential for the research of the Alzheimer's disease[3].

  • CAS Number: 2504147-81-1
  • MF: C43H65F3N8O16
  • MW: 1007.02
  • Catalog: Beta-secretase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ONO-8590580

ONO-8590580 is a GABAA α5 negative allosteric modulator.

  • CAS Number: 1802661-73-9
  • MF: C21H21FN6
  • MW: 376.43
  • Catalog: GABA Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(Rac)-Monepantel-d5

(Rac)-Monepantel-d5 is deuterium labeled Monepantel. Monepantel is organic anthelmintic, and acts as a positive allosteric modulator of a nematode-specific clade of nicotinic acetylcholine receptor (nAChR) subunits.

  • CAS Number: 2747918-33-6
  • MF: C20H8D5F6N3O2S
  • MW: 478.42
  • Catalog: nAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A