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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Autophagy >
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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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Varenicline (Hydrochloride)

Varenicline Hcl(CP 526555;Champix) is a nicotinic receptor partial agonist; it stimulates nicotine receptors more weakly than nicotine itself does.IC50 value:Target: nAChRVarenicline(CP 526555; Champix; Chantix) is a prescription medication used to treat smoking addiction. As a partial agonist it both reduces cravings for and decreases the pleasurable effects of cigarettes and other tobacco products. Through these mechanisms Varenicline(CP 526555; Champix; Chantix) can assist some patients to quit smoking.

  • CAS Number: 230615-23-3
  • MF: C13H14ClN3
  • MW: 247.723
  • Catalog: nAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bemegride

Bemegride is a central nervous system stimulant and antidote for barbiturate poisoning.target: GABAA receptor Bemegride has an antagonistic action on the GABAA receptor, suppressing both GABA- and pentobarbitone-evoked whole-cell currents to similar extents. [1] Long-term oral administration to the rat of barbitone, alone or together with the analeptics bemegride or pentylenetetrazol, show that the intensity of the withdrawal syndrome generally parallels the degree of associated CNS depression. [2]

  • CAS Number: 64-65-3
  • MF: C8H13NO2
  • MW: 155.194
  • Catalog: GABA Receptor
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 282.0±9.0 °C at 760 mmHg
  • Melting Point: 126-127 °C(lit.)
  • Flash Point: 125.8±18.9 °C

(S)-(-)-5-Fluorowillardiine

(S)-(-)-5-Fluorowillardiine is a potent and specific AMPAR agonist.

  • CAS Number: 140187-23-1
  • MF: C7H8FN3O4
  • MW: 217.15500
  • Catalog: iGluR
  • Density: 1.64 g/cm3
  • Boiling Point: N/A
  • Melting Point: 235ºC
  • Flash Point: N/A

MAO A/HSP90-IN-1

MAO A/HSP90-IN-1 (4-b) is a MAO A/HSP90 dual inhibitor with IC50 value of 1.77 μM and 0.019 μM in Glioblastoma (GBM) GL26 cells and HSP90α, respectively. MAO A/HSP90-IN-1 (4-b) can inhibit MAO A activity, HSP90 binding and the expression of HER2 and phospho-Akt to inhibit the growth of GBM, they also reduce PD-L1 expression, which inhibits T cell activation. MAO A/HSP90-IN-1 (4-b) have potential to inhibit tumor immune escape. MAO A/HSP90-IN-1 (4-b) can be used for brain tumor-related diseases research[1].

  • CAS Number: 2927489-95-8
  • MF: C24H29ClN2O4
  • MW: 444.95
  • Catalog: HSP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Onzigolide

Onzigolide (BIM-23A760), a chimeric dopamine-somatostatin compound, shows potent agonist activity at both DA type 2 (D2R) and SST type 2 (SSTR2) receptors[1][2].

  • CAS Number: 778630-77-6
  • MF: C86H116N16O12S4
  • MW: 1694.20
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CGRP antagonist 2

CGRP antagonist 2 is a CGRP receptor antagonist. CGRP antagonist 2 can be used for pain relief[1].

  • CAS Number: 866086-05-7
  • MF: C35H47N5O6
  • MW: 633.78
  • Catalog: CGRP Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SIB-1553A

SIB-1553A hydrochloride is an orally bioavailable nicotinic acetylcholine receptors (nAChRs) agonist, with selectivity for β4 subunit-containing nAChRs. SIB-1553A hydrochloride is also a selective neuronal nAChR ligand. SIB-1553A hydrochloride is a cognitive enhancer, and has therapeutic potential for the symptomatic treatment of Alzheimer’s disease and other cognitive disorders[1][2].

  • CAS Number: 191611-89-9
  • MF: C13H20ClNOS
  • MW: 273.822
  • Catalog: nAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

YM-58790 free base

YM-58790 free base is a potent antagonist of mAChR. YM-58790 free base binds M1, M2, M3 with Ki values of 28 nM, 260 nM, and 15 nM. YM-58790 free base exhibits potent inhibitory activity on bladder pressuer in reflexly-evoked rhythmic contraction in rats[1].

  • CAS Number: 168830-70-4
  • MF: C27H31N3O2
  • MW: 429.55
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MK-3207

MK-3207 is a potent and orally bioavailable CGRP receptor antagonist (IC50= 0.12 nM; Ki value= 0.024 nM); highly selective versus human AM1, AM2, CTR, and AMY3.IC50 Value: 0.024 nM (Ki, Human CGRP) [1]In common with other CGRP receptor antagonists, MK-3207 displays lower affinity for human CGRP receptors from other species, including canine and rodent.in vitro: MK-3207 is a potent antagonist of the human and rhesus monkey CGRP receptors (K(i) = 0.024 nM). in vivo: MK-3207 produced a concentration-dependent inhibition of dermal vasodilation, with plasma concentrations of 0.8 and 7 nM required to block 50 and 90% of the blood flow increase, respectively. The tritiated analog [3H]MK-3207 was used to study the binding characteristics on the human CGRP receptor. [3H]MK-3207 displayed reversible and saturable binding (K(D) = 0.06 nM), and the off-rate was determined to be 0.012 min(-1), with a t(1/2) value of 59 min [1]. After the first interim analysis, the two lowest MK-3207 doses (2.5, 5?mg) were identified as showing insufficient efficacy. Per the pre-specified adaptive design decision rule, only the 2.5-mg group was discontinued and the five highest doses (5, 10, 20, 50, 100?mg) were continued into the second stage [2].Clinical trial: MK-3207 for the treatment of acute migraines. Phase 2b

  • CAS Number: 957118-49-9
  • MF: C31H29F2N5O3
  • MW: 557.591
  • Catalog: CGRP Receptor
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 812.1±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 444.9±34.3 °C

GSK-LSD1 Dihydrochloride

GSK-LSD1 Dihydrochloride is a potent, selective and irreversible lysine specific demethylase 1 (LSD1) inhibitor with an IC50 of 16 nM.

  • CAS Number: 2102933-95-7
  • MF: C14H22Cl2N2
  • MW: 289.24
  • Catalog: Histone Demethylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Amisulpride

Amisulpride is a dopamine D2/D3 receptor antagonist with Kis of 2.8 and 3.2 nM for human dopamine D2 and D3, respectively.

  • CAS Number: 71675-85-9
  • MF: C17H27N3O4S
  • MW: 369.479
  • Catalog: Dopamine Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 558.9±50.0 °C at 760 mmHg
  • Melting Point: 124-128ºC
  • Flash Point: 291.8±30.1 °C

Endomorphin-2

Endomorphin 2, a high affinity, highly selective agonist of the μ-opioid receptor, displays reasonable affinities for kappa3 binding sites, with Ki value between 20 and 30 nM.

  • CAS Number: 141801-26-5
  • MF: C32H37N5O5
  • MW: 571.66700
  • Catalog: Peptides
  • Density: 1.292g/cm3
  • Boiling Point: 972.4ºC at 760mmHg
  • Melting Point: 130-131℃
  • Flash Point: 541.9ºC

Protriptyline (N-methyl-d3) (hydrochloride)

Protriptyline (N-Methyl-d3) hydrochloride is the deuterium labeled Protriptyline hydrochloride. Protriptyline hydrochloride is a tricyclic antidepressant (TCA), specifically a secondary amine, for the treatment of depression and ADHD. Unique among the TCAs, protriptyline tends to be energizing instead of sedating, used for narcolepsy to achieve a wakefulness-promoting effect[1].

  • CAS Number: 1435934-21-6
  • MF: C19H19D3ClN
  • MW: 266.40
  • Catalog: AChE
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

picraline

Picraline is a natural alkaloid that targets opioid receptors with binding affinities with Ki values of 132 μM, 2.38 μM and 98.8 μM for μOR, κOR and δOR, respectively[1].

  • CAS Number: 2671-32-1
  • MF: C23H26N2O5
  • MW: 410.46
  • Catalog: Opioid Receptor
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 548.0±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 285.2±30.1 °C

N'-benzylpivalohydrazide

Pivalylbenzhydrazine (Pivhydrazine) is a potent monoamine oxidase (MAO) inhibitor. Pivalylbenzhydrazine decreases cartilage growth in normal rats. Pivalylbenzhydrazine can be used in research of depression[1].

  • CAS Number: 306-19-4
  • MF: C12H18N2O
  • MW: 206.28400
  • Catalog: Monoamine Oxidase
  • Density: 1.015g/cm3
  • Boiling Point: 296.1ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 105.6ºC

(S)-Bexicaserin

(S)-Bexcaserin (compound 2) is a 5-HT2C receptor agonist with potential for studying obesity and psychiatric-related diseases[1].

  • CAS Number: 2035818-21-2
  • MF: C15H19F2N3O
  • MW: 295.33
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Donitriptan monohydrochloride

Donitriptan hydrochloride (F-11356) is a potent, high efficacy agonist at 5-HT1B/1D receptors with pKis of 9.4 and 9.3, respectively[1].

  • CAS Number: 170911-68-9
  • MF: C23H26ClN5O2
  • MW: 439.94
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: 727.1ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 393.6ºC

Venlafaxine-d10 hydrochloride

Venlafaxine-d10 (Wy 45030-d10) is the deuterium labeled Venlafaxine hydrochloride. Venlafaxine (Wy 45030) hydrochloride is an orally active, potent serotonin (5-HT)/norepinephrine (NE) reuptake dual inhibitor. Venlafaxine is an antidepressant[1][2].

  • CAS Number: 1216539-56-8
  • MF: C17H18ClD10NO2
  • MW: 323.92433778
  • Catalog: Serotonin Transporter
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SYM 2081

SYM 2081 is a high-affinity ligand and potent, selective agonist of kainate receptors, inhibits [3H]-kainate binding with an IC50 of 35 nM, almost 3000- and 200-fold selectivity for kainate receptors over AMPA and NMDA receptors respectively[1].

  • CAS Number: 31137-74-3
  • MF: C6H11NO4
  • MW: 161.16
  • Catalog: iGluR
  • Density: N/A
  • Boiling Point: 329.4ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 153ºC

AS 19

AS19 is a potent, selective 5-HT7 receptor agonist with an IC50 value of 0.83 nM and a Ki of 0.6 nM. AS19 is selective for 5-HT7 over 5-HT1A, 5-HT1B, 5-HT1D, and 5-HT5A receptors (Kis = 89.7 nM, 490 nM, 6.6 nM and 98.5 nM, respectively). AS19 enhances memory consolidation and reverses Scopolamine- or Dizocilpine-induced amnesia[1][2][3].

  • CAS Number: 1000578-26-6
  • MF: C18H25N3
  • MW: 283.411
  • Catalog: 5-HT Receptor
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 413.3±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 203.7±28.7 °C

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: 286930-02-7
  • MF: C26H37NO3
  • MW: 412.58500
  • Catalog: mAChR
  • Density: 1.043
  • Boiling Point: 518.9ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 267.6ºC

Penconazole-d7

Penconazole-d7 is the deuterium labeled Penconazole[1]. Penconazole is a typical triazole fungicide, and mainly applied on apples, grapes, and vegetables to control powdery mildew. Penconazole inhibits sterol biosynthesis in fungi. Penconazole decrease AChE activity in the cerebrum and cerebellum of rats[2][3].

  • CAS Number: 1628110-84-8
  • MF: C13H8D7CL2N3
  • MW: 291.23
  • Catalog: Fungal
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 415.3±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 204.9±31.5 °C

Yoda 1

GlyT2-IN-1 is a glycine transporters GLYT2 inhibitor.Target: GLYT2The Glycine Transporter GlyT2 Controls the Dynamics of Synaptic Vesicle Refilling in Inhibitory Spinal Cord Neurons. GlyT2-IN-1 is a novel agonist of the mechanotransduction channel Piezo1, eliciting Ca2+ flux in Piezo1- but not vector-transfected cells.

  • CAS Number: 448947-81-7
  • MF: C13H8Cl2N4S2
  • MW: 355.265
  • Catalog: GlyT
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 538.4±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 279.4±32.9 °C

Dolasetron (Mesylate hydrate)

Dolasetron(MDL-73147) is a serotonin 5-HT3 receptor antagonist used to treat nausea and vomiting following chemotherapy.

  • CAS Number: 878143-33-0
  • MF: C20H26N2O7S
  • MW: 438.49
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 178 °C
  • Flash Point: N/A

Oleoyl-D-lysine

Oleoyl-D-lysine is a selective Glycine Transporter-2 (GlyT2) inhibitor based on lipid. Oleoyl-D-lysine reverses neuropathic pain in mice, shows antidrowsiness effect on chronic neuropathic pain. Oleoyl-D-lysine is safe and effective without respiratory depression[1].

  • CAS Number: 2240164-55-8
  • MF: C24H46N2O3
  • MW: 410.63
  • Catalog: iGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PRX933 hydrochloride

PRX933 hydrochloride is a 5-HT2c receptor agonist extracted from patent WO 2014140631 A1.

  • CAS Number: 639029-42-8
  • MF: C16H22ClN5O2
  • MW: 351.83
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Enzacamene

4-Methylbenzylidene camphor(4-MBC; Enzacamene)is an organic camphor derivative that is used in the cosmetic industry for its ability to protect the skin against UV, specifically UV B radiation.

  • CAS Number: 36861-47-9
  • MF: C18H22O
  • MW: 254.367
  • Catalog: AChE
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 371.9±22.0 °C at 760 mmHg
  • Melting Point: 66-68°C
  • Flash Point: 168.9±13.2 °C

69-23-8 (free base)

Fluphenazine dimaleate is a potent, orally active phenothiazine-based dopamine receptor antagonist. Fluphenazine dimaleate blocks neuronal voltage-gated sodium channels. Fluphenazine dimaleate acts primarily through antagonism of postsynaptic dopamine-2 receptors in mesolimbic, nigrostriatal, and tuberoinfundibular neural pathways. Fluphenazine dimaleate can antagonize Methylphenidate-induced stereotyped gnawing and inhibit climbing behaviour in mice. Fluphenazine dimaleate can be used for researching psychosis and painful peripheral neuropathy associated with diabetes and has potential to inhibit SARS-CoV-2[1][2][3][4][6].

  • CAS Number: 3093-66-1
  • MF: C26H30F3N3O5S
  • MW: 553.59400
  • Catalog: SARS-CoV
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

S 24795

S 24795 is a partial agonist of α7 nAChR and improves mnemonic function in aged mice for the treatment of aging-related memory disturbances[1].

  • CAS Number: 304679-75-2
  • MF: C14H13BrINO
  • MW: 418.06800
  • Catalog: nAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(D-Pen2,Pen5)-Enkephalin

[DPen2, Pen5] Enkephalin is a δ-opioid receptor selective analog of [Leu5]-Enkephalin (HY-P0288)[1].

  • CAS Number: 88373-72-2
  • MF: C30H39N5O7S2
  • MW: 645.790
  • Catalog: Opioid Receptor
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 1038.6±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 581.9±34.3 °C