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 >
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Apoptosis >
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Autophagy >
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ERK JNK KLF MAP3K MAP4K MAPKAPK2 (MK2) MEK Mixed Lineage Kinase MNK p38 MAPK Raf Ribosomal S6 Kinase (RSK)
Membrane Transporter/Ion Channel >
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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
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Tulrampator

Tulrampator (CX-1632) is an orally bioavailable positive allosteric modulator of AMPA receptor (AMPAR)[1]. Antidepressant[1].

  • CAS Number: 1038984-31-4
  • MF: C20H17FN4O3
  • MW: 380.37
  • Catalog: iGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(R)-VU 6008667

(R)-VU 6008667, an active enantiomer of VU6008667, is a orally active acetylcholine receptor subtype 5 (M5 NAM) inhibitor with IC50 values of 1.2 μM (human) and 1.6 μM (rat), respectively. (R)-VU6008667 is selective for M5 over M1-4, high CNS penetration[1].

  • CAS Number: 2097818-14-7
  • MF: C24H17ClF2N2O2
  • MW: 438.85
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

5,7-Dimethoxyluteolin

5,7-Dimethoxyluteolin, a 5,7-dimethylluteolin derivative, is a dopamine transporter (DAT) activator with an EC50 of 3.417 μM[1].

  • CAS Number: 90363-40-9
  • MF: C17H14O6
  • MW: 314.28900
  • Catalog: Dopamine Transporter
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cassiaside B2

Cassiaside B2 is a protein tyrosine phosphatase 1B (PTP1B) and human monoamine oxidase A (hMAO-A) inhibitor. Cassiaside B2 possesses antiallergic and is a 5-HT2C receptor agonist[1][2].[3]..

  • CAS Number: 218155-40-9
  • MF: C39H52O25
  • MW: 920.82
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

[D-Pro4,D-Trp7,9,Nle11]-Substance P (4-11)

[D-Pro4,D-Trp7,9,Nle11] Substance P (4-11) is a potent neurokinin NK1 antagonist. [D-Pro4,D-Trp7,9,Nle11] Substance P (4-11) inhibits the effects of gold-protein-substance P (GPSP) and substance P (SP)[1].

  • CAS Number: 89430-34-2
  • MF: C58H77N13O10
  • MW: 1116.31000
  • Catalog: Neurokinin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Fremanezumab

Fremanezumab (TEV-48125) is a humanized IgG2a monoclonal antibody that selectively and potently binds to calcitonin gene-related peptide (CGRP). CGRP is a 37-amino acid neuropeptide involved in central and peripheral pathophysiological events of migraine. Fremanezumab has the potential for chronic migraine research[1].

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

GBR 12783 dihydrochloride

GBR 12783 dihydrochloride is a specific, potent and selective dopamine uptake inhibitor that inhibits the [3H]dopamine uptake by rat and mice striatal synaptosomes with IC50s of 1.8 nM and 1.2 nM, respectively. GBR 12783 dihydrochloride can improve memory performance and increase hippocampal acetylcholine release in rats[1][2].

  • CAS Number: 67469-75-4
  • MF: C28H34Cl2N2O
  • MW: 485.48800
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CGP 35348

CGP 35348 is a selective, brain penetrant, centrally active GABAB receptor antagonist with an EC50 of 34 μM. CGP 35348 shows affinity for the GABAB receptor only[1]. CGP 35348 has a potential to improve neuromuscular coordination and spatial learning in albino mouse following neonatal brain damage[2].

  • CAS Number: 123690-79-9
  • MF: C8H20NO4P
  • MW: 225.22
  • Catalog: GABA Receptor
  • Density: 1.131g/cm3
  • Boiling Point: 400.5ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 196ºC

Tolterodine tartrate

Tolterodine Tartrate(PNU-200583E; Kabi-2234) is a potent muscarinic receptor antagonists that show selectivity for the urinary bladder over salivary glands in vivo. IC50 Value:Target: mAChRin vitro: Carbachol-induced contractions of isolated guinea pig bladder were effectively inhibited by tolterodine (IC50 14 nM) and 5-HM (IC50 5.7 nM). The IC50 values were in the microM range and the antimuscarinic potency of tolterodine was 27, 200 and 370-485 times higher, respectively, than its potency in blocking histamine receptors, alpha-adrenoceptors and calcium channels. The active metabolite, 5-HM, was >900 times less potent at these sites than at bladder muscarinic receptors [1].in vivo: Tolterodine was extensively metabolized in vivo [2]. In the passive-avoidance test, tolterodine at 1 or 3 mg/kg had no effect on memory; the latency to cross and percentage of animals crossing were comparable to controls. In contrast, scopolamine induced a memory deficit; the latency to cross was decreased, and the number of animals crossing was increased [3].

  • CAS Number: 124937-52-6
  • MF: C26H37NO7
  • MW: 475.574
  • Catalog: mAChR
  • Density: 1.003 g/cm3
  • Boiling Point: 442.2ºC at 760 mmHg
  • Melting Point: 205-210ºC
  • Flash Point: 192.1ºC

Kynurenic acid sodium salt

Kynurenic acid, an endogenous tryptophan metabolite, is a broad-spectrum antagonist targeting NMDA, glutamate, α7 nicotinic acetylcholine receptor. Kynurenic acid is also a selective ligand of the GPR35 receptor.

  • CAS Number: 2439-02-3
  • MF: C10H7NNaO3
  • MW: 212.16
  • Catalog: iGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Aftin-4

Aftin-4 is an Amyloid-β42 (Aβ42) inducer.

  • CAS Number: 866893-90-5
  • MF: C20H28N6O
  • MW: 368.47600
  • Catalog: Amyloid-β
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Milnacipran hydrochloride

Milnacipran hydrochloride is a serotonin-norepinephrine reuptake inhibitor (SNRI) used in the clinical treatment of fibromyalgia.Target: SNRIMilnacipran (Ixel, Savella, Dalcipran, Toledomin) is a serotonin-norepinephrine reuptake inhibitor (SNRI) used in the clinical treatment of fibromyalgia. It is not approved for the clinical treatment of major depressive disorder in the USA, but it is in other countries.Milnacipran inhibits the reuptake of serotonin and norepinephrine in an approximately 1:3 ratio, respectively; in practical use this means a relatively balanced action upon bothneurotransmitters. Increasing both neurotransmitters concentration simultaneously works synergistically to treat both depression and fibromyalgia. Milnacipran exerts no significant actions onH1, α1, D1, D2, and mACh receptors, as well as on benzodiazepine and opioid binding sites. Milnacipran is well absorbed after oral dosing and has a bioavailability of 85%. Meals do not have an influence on the rapidity and extent of absorption. Peak plasma concentrations are reached 2 hours after oral dosing. The elimination half-life of 8 hours is not increased by liver impairment and old age, but by significant renal disease. Milnacipran is conjugated to the inactive glucuronide and excreted in the urine as unchanged drug and conjugate. Only traces of active metabolites are found.

  • CAS Number: 101152-94-7
  • MF: C15H23ClN2O
  • MW: 282.809
  • Catalog: Serotonin Transporter
  • Density: N/A
  • Boiling Point: 393ºC at 760 mmHg
  • Melting Point: 179-181ºC
  • Flash Point: N/A

Zamifenacin fumarate

Zamifenacin fumarate (UK-76654 fumarate) is a potent gut-selective muscarinic M3 receptor antagonist. Zamifenacin significantly reduces colonic motility in irritable bowel syndrome[1].

  • CAS Number: 127308-98-9
  • MF: C31H33NO7
  • MW: 531.59600
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: 700.2ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 377.3ºC

Anabasine

Anabasine is a nicotinic receptor agonist.

  • CAS Number: 494-52-0
  • MF: C10H14N2
  • MW: 162.23200
  • Catalog: nAChR
  • Density: 1,0455 g/cm3
  • Boiling Point: 270-272°C
  • Melting Point: 9°C
  • Flash Point: 93°C

Scyliorhinin II

Scyliorhinin II is a selective neurokinin-3 receptor agonist, with a Ki of 2.5 nM for neurokinin-3 receptor in rat cerebral cortex.

  • CAS Number: 112748-19-3
  • MF: C77H119N21O26S3
  • MW: 1851.089
  • Catalog: Peptides
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 1817.4±75.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 1052.9±37.1 °C

Akuammidine

Akuammidine, isolated from the seeds of Picralima nitida, shows a preference for μ-opioid binding sites with Ki values of 0.6, 2.4 and 8.6 μM at μ-, σ- and κ-opioid binding sites, respectively. Akuammidine possesses anti-inflammatory and anti-asthmatic properties[1][2].

  • CAS Number: 639-36-1
  • MF: C21H24N2O3
  • MW: 352.427
  • Catalog: Opioid Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 513.0±50.0 °C at 760 mmHg
  • Melting Point: 243-246℃
  • Flash Point: 264.0±30.1 °C

Isoguvacine Hydrochloride

Isoguvacine hydrochloride is a GABA receptor agonist.

  • CAS Number: 68547-97-7
  • MF: C6H10ClNO2
  • MW: 163.60200
  • Catalog: GABA Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Anagyrine hydrochloride

Anagyrine ((-)-Anagyrine) hydrochloride is a quinolizidine alkaloid that has been found in Lupinus albus. Anagyrine hydrochloride binds to muscarinic and nicotinic acetylcholine receptors with IC50 values of 132 and 2096 µM respectively. Anagyrine hydrochloride is a potent and effective desensitizer of nAChR, and Anagyrine hydrochloride can directly, without metabolism, desensitize nAChR[1][2][3].

  • CAS Number: 74195-83-8
  • MF: C15H21ClN2O
  • MW: 280.79
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AC-42

AC-42 is a poent M1 muscarinic selective allosteric agonist with EC50s of 805 nM and 220 nM for human wild-type and Y381A mutated M1 receptors, respectively[1].

  • CAS Number: 244291-63-2
  • MF: C20H31NO
  • MW: 301.47
  • Catalog: mAChR
  • Density: 0.958±0.06 g/cm3(Predicted)
  • Boiling Point: 427.5±28.0 °C(Predicted)
  • Melting Point: N/A
  • Flash Point: N/A

4-(6-Bromo-2-benzothiazolyl)benzenamine

4-(6-Bromo-2-benzothiazolyl)benzenamine is a β-amyloid PET (positron emission tomography) tracer that can be used in the diagnosis of neurological diseases, such as Alzheimer's and Down's syndrome.

  • CAS Number: 566169-97-9
  • MF: C13H9BrN2S
  • MW: 305.19300
  • Catalog: Amyloid-β
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Monomyristin

1-Monomyristin, extracted from Serenoa repens, inhibits the hydrolysis of 2-oleoylglycerol (IC50=32 μM) and fatty acid amide hydrolase (FAAH) activity (IC50=18 μM). 1-Monomyristin shows antibacterial activity against Staphylococcus aureus and Aggregatibacter actinomycetemcomitans and also antifungal activity against Candida albicans[1][2][3].

  • CAS Number: 589-68-4
  • MF: C17H34O4
  • MW: 302.449
  • Catalog: Bacterial
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 424.8±25.0 °C at 760 mmHg
  • Melting Point: 68-70ºC
  • Flash Point: 141.3±16.7 °C

Clozapine-d4

Clozapine-d4 (HF 1854-d4) is the deuterium labeled Clozapine. Clozapine is an antipsychotic used for the research of schizophrenia. Clozapine has high affinity for a number of neuroreceptors[1][2][3][4][5].

  • CAS Number: 204395-52-8
  • MF: C18H15D4ClN4
  • MW: 330.848
  • Catalog: 5-HT Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 489.2±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 249.6±31.5 °C

Dexpramipexole

Dexpramipexole(KNS-760704), also known as R-(+)-Pramipexole, is a neuroprotective agent and weak non-ergoline dopamine agonist. IC50 Value:Target: Dopamine ReceptorDexpramipexole has been found to have neuroprotective effects and is being investigated for treatment of amyotrophic lateral sclerosis (ALS). Dexpramipexole reduces mitochondrial reactive oxygen species (ROS) production, inhibits the activation of apoptotic pathways, and increase cell survival in response to a variety of neurotoxins and β-amyloid neurotoxicity. Compared to the S-(-) isomer, Dexpramipexole has much lower dopamine agonist activity.

  • CAS Number: 104632-28-2
  • MF: C10H17N3S
  • MW: 211.331
  • Catalog: Dopamine Receptor
  • Density: 1.17±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: 270-272ºC
  • Flash Point: N/A

Sarmazenil

Sarmazenil is a benzodiazepine receptor antagonist.

  • CAS Number: 78771-13-8
  • MF: C15H14ClN3O3
  • MW: 319.74300
  • Catalog: GABA Receptor
  • Density: 1.43g/cm3
  • Boiling Point: 554ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 288.9ºC

PF0346275

A potent, selective, orally available GlyT1 inhibitor with Ki of 11.6 nM, without activity against GlyT2 (IC50>10 uM); demonstrates potent activity in elevating CSF levels of glycine in vivo (ED200, 3.5 mg/kg).

  • CAS Number: 1173239-39-8
  • MF: C19H22ClFN4O
  • MW: 449.777
  • Catalog: GlyT
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

4-Acetamidobutanoic acid

4-Acetamidobutanoic acid (N-acetyl GABA) is a γ-aminobutyric acid (GABA) derivative.

  • CAS Number: 3025-96-5
  • MF: C6H11NO3
  • MW: 145.15600
  • Catalog: GABA Receptor
  • Density: 1.133 g/cm3
  • Boiling Point: 405.4ºC at 760 mmHg
  • Melting Point: 128-131 °C
  • Flash Point: 199ºC

T 82

T 82 is a potent 5-HT3 antagonist and acetylcholinesterase (AChE) inhibitor, used for treatment of Alzheimer's Disease.

  • CAS Number: 252264-92-9
  • MF: C26H29N3O2.1/2C4H4O4
  • MW: 473.56
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Withanone

Withanone is an active constituent from Withania somnifera roots with multifunctional neuroprotective effect in alleviating cognitive dysfunction. Withanone affords protection against N-methyl-D-aspartate (NMDA)-induced excitotoxicity in Neuron-like cells[1][2].

  • CAS Number: 27570-38-3
  • MF: C28H38O6
  • MW: 470.59800
  • Catalog: iGluR
  • Density: 1.264g/cm3
  • Boiling Point: 653.7ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 216.5ºC

Anrikefon acetate

Anrikefon (HSK21542) acetate is a kappa opioid receptor agonist with analgesic effect[1].

  • CAS Number: 2584931-05-3
  • MF: C41H61N7O7
  • MW: 763.97
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tolterodine-L-tartrate

Tolterodine(PNU-200583) is a potent muscarinic receptor antagonists that show selectivity for the urinary bladder over salivary glands in vivo. IC50 Value:Target: mAChRin vitro: Carbachol-induced contractions of isolated guinea pig bladder were effectively inhibited by tolterodine (IC50 14 nM) and 5-HM (IC50 5.7 nM). The IC50 values were in the microM range and the antimuscarinic potency of tolterodine was 27, 200 and 370-485 times higher, respectively, than its potency in blocking histamine receptors, alpha-adrenoceptors and calcium channels. The active metabolite, 5-HM, was >900 times less potent at these sites than at bladder muscarinic receptors [1].in vivo: Tolterodine was extensively metabolized in vivo [2]. In the passive-avoidance test, tolterodine at 1 or 3 mg/kg had no effect on memory; the latency to cross and percentage of animals crossing were comparable to controls. In contrast, scopolamine induced a memory deficit; the latency to cross was decreased, and the number of animals crossing was increased [3].

  • CAS Number: 124937-51-5
  • MF: C22H31NO
  • MW: 325.488
  • Catalog: mAChR
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 442.2±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 192.1±27.4 °C