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Neuronal Signaling

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Neuronal Signaling Inhibitors, Agonists, Screening Libraries www.MedChemExpress.com Neuronal Signaling 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. www.MedChemExpress.com 1 Inhibitors, Agonists, Screening Libraries www.MedChemExpress.com Target List in Neuronal Signaling • 5-HT Receptor 3 • Serotonin Transporter 143 • AChE 27 • γ-secretase 149 • Adenosine Kinase 32 • Amyloid-β 34 • Beta-secretase 40 • CaMK 43 • CGRP Receptor 47 • COMT 50 • Dopamine Receptor 52 • Dopamine Transporter 67 • FAAH 70 • GABA Receptor 73 • GlyT 84 • iGluR 86 • Imidazoline Receptor 98 • mAChR 100 • Melanocortin Receptor 113 • Melatonin Receptor 116 • Monoamine Oxidase 118 • nAChR 123 • Neurokinin Receptor 129 • Opioid Receptor 135 2 Tel: 609-228-6898 Fax: 609-228-5909 Email: [email protected] 5-HT Receptor Serotonin Receptor;5-hydroxytryptamine Receptor 5-HT receptors (Serotonin receptors) are a group of G protein-coupled receptors (GPCRs) and ligand-gated ion channels (LGICs) found in the central and peripheral nervous systems. Type: 5-HT1, 5-HT2, 5-HT3, 5-HT4, 5-HT5, 5-HT6, 5-HT7. They mediate both excitatory and inhibitory neurotransmission. The serotonin receptors are activated by the neurotransmitter serotonin, which acts as their natural ligand. The serotonin receptors modulate the release of many neurotransmitters, as well as many hormones. The serotonin receptors influence various biological and neurological processes such as aggression, anxiety, appetite, cognition, learning, memory, mood, nausea, sleep, andthermoregulation. The serotonin receptors are the target of a variety of pharmaceutical drugs, including many antidepressants, antipsychotics, anorectics,antiemetics, gastroprokinetic agents, antimigraine agents, hallucinogens, and entactogens. www.MedChemExpress.com 3 5-HT Receptor Inhibitors & Modulators (4E)-SUN9221 (R,R)-Palonosetron Hydrochloride Cat. No.: HY-U00367 Cat. No.: HY-A0021C Bioactivity: (4E)-SUN9221 is a potent antagonist of α1-adrenergic receptor Bioactivity: (R,R)-Palonosetron Hydrochloride is the active enantiomer of and 5-HT2 receptor, with antihypertensive and anti-platelet Palonosetron. aggregation activities. Purity: >98% Purity: 99.61% Clinical Data: No Development Reported Clinical Data: No Development Reported Size: 1 mg, 5 mg, 10 mg, 20 mg Size: 2 mg, 5 mg, 10 mg (Z)-Thiothixene 5-HT1A modulator 1 Cat. No.: HY-108324 Cat. No.: HY-100290 Bioactivity: (Z)-Thiothixene is an antagonist of serotonergic receptor Bioactivity: 5-HT1A modulator 1 displays very high affinities for the extracted from patent US 20150141345 A1. 5HT1A, adrenergic α1 and dopamine D2 receptor with IC50s of 2 ±0.3 nM, 10 ± 3 nM and 40 ±9 nM, respectively. Purity: 99.14% Purity: >98% Clinical Data: No Development Reported Clinical Data: No Development Reported Size: 10mM x 1mL in DMSO, Size: 1 mg, 5 mg, 10 mg 5 mg, 10 mg, 25 mg 5-HT2 antagonist 1 5-HT2A antagonist 1 Cat. No.: HY-U00365 Cat. No.: HY-U00286 Bioactivity: 5-HT2 antagonist 1 is a potent antagonist of 5-HT2 receptor, Bioactivity: 5-HT2A antagonist 1 is a 5-HT2A antagonist extracted from with weak α1 adrenoceptor blocking activity. patent US5728835A and JP 1007727. 5-HT2A antagonist 1 may be useful in treatment of gastrointestinal disorders circulatory disorders. Purity: >98% Purity: >98% Clinical Data: No Development Reported Clinical Data: No Development Reported Size: 1 mg, 5 mg, 10 mg, 20 mg Size: 1 mg, 5 mg, 10 mg, 20 mg 5-HT3 antagonist 1 5-HT3 antagonist 2 Cat. No.: HY-U00368 Cat. No.: HY-U00408 Bioactivity: 5-HT3 antagonist 1 is a potent and selective antagonist of Bioactivity: 5-HT3 antagonist 2 is a 5-HT3 receptor antagonist. serotonin 3 (5-HT3) receptor. Purity: >98% Purity: >98% Clinical Data: No Development Reported Clinical Data: No Development Reported Size: 1 mg, 5 mg, 10 mg Size: 1 mg, 5 mg, 10 mg, 20 mg 5-HT3-In-1 5-HT4 antagonist 1 Cat. No.: HY-U00413 Cat. No.: HY-100170 Bioactivity: 5-HT3-In-1 is extracted from patent EP0748807A1, compound Bioactivity: 5-HT4 antagonist 1 is a 5-HT4 receptor antagonist with a example 8. It shows 5-HT3 inhibition activity. pKi of 9.6. Purity: >98% Purity: >98% Clinical Data: No Development Reported Clinical Data: No Development Reported Size: 1 mg, 5 mg, 10 mg, 20 mg Size: 1 mg, 5 mg, 10 mg 4 Tel: 609-228-6898 Fax: 609-228-5909 Email: [email protected] 5-HT6/7 antagonist 1 5-HT7 agonist 1 Cat. No.: HY-101622 Cat. No.: HY-109527 Bioactivity: 5-HT6/7 antagonist 1 is a multifunctional ligand that Bioactivity: 5-HT7 agonist 1 is a selective 5-HT7 receptor agonist, with antagonizes 5-HT6/7/2A and D2 receptors, without an IC50 of 222.93 nM, can be used for the 5-HT7 receptor interacting with M1 receptors and hERG channels. related disease, such as CNS disorders. Purity: >98% Purity: >98% Clinical Data: No Development Reported Clinical Data: No Development Reported Size: 250 mg, 500 mg Size: 250 mg, 500 mg 5HT6-ligand-1 8-OH-DPAT Cat. No.: HY-U00126 (8-Hydroxy-DPAT) Cat. No.: HY-112061 Bioactivity: 5HT6-ligand-1 is a potent 5-HT6 receptor ligand with a Ki of Bioactivity: 8-OH-DPAT is a potent and selective 5-HT agonist, with a pIC of 8.19 for 5-HT1A and a K of 466 nM for 5-HT7; 1.43 nM. 50 i 8-OH-DPAT weakly binds to 5-HT1B (pIC 50, 5.42), 5-HT (pIC 50 <5). Purity: >98% Purity: 98.0% Clinical Data: No Development Reported Clinical Data: No Development Reported Size: 1 mg, 5 mg, 10 mg, 20 mg Size: 10mM x 1mL in DMSO, 5 mg, 10 mg, 25 mg, 50 mg, 100 mg Abaperidone Adoprazine Cat. No.: HY-101619 (SLV313) Cat. No.: HY-14782 Bioactivity: Abaperidone is a potent antagonist of 5-HT2Areceptor and Bioactivity: Adoprazine, a potential atypical antipsychotic bearing potent D2 receptor antagonist and 5-HT1A receptor agonist properties. dopamine D2 receptor with IC50s of 6.2 and 17 nM. Purity: >98% Purity: 98.13% Clinical Data: No Development Reported Clinical Data: Phase 1 Size: 1 mg, 5 mg, 10 mg, 20 mg Size: 10mM x 1mL in DMSO, 5 mg, 10 mg, 50 mg Agomelatine Agomelatine hydrochloride (S-20098) Cat. No.: HY-17038 (S-20098 hydrochloride) Cat. No.: HY-17038A Bioactivity: Agomelatine is a competitive antagonist of human and porcine Bioactivity: Agomelatine hydrochloride is a antidepressant, which is serotonin (5-HT2C) receptors (pKi = 6.2 and 6.4, respectively) classified as a norepinephrine-dopamine disinhibitor (NDDI) as well as human 5-HT2B receptors (pKi = 6.6). IC50 value: 6.2 due to its antagonism of the 5-HT2C receptor. (pKi, 5-HT2c); 6.6 (pKi, 5-HT2b) Target: 5-HT2C Receptor; 5-HT2B receptor It is classified as a norepinephrine-dopamine… Purity: 99.88% Purity: 99.49% Clinical Data: Launched Clinical Data: Launched Size: 10mM x 1mL in DMSO, Size: 10mM x 1mL in DMSO, 5 mg, 10 mg, 50 mg, 100 mg 5 mg, 10 mg, 50 mg, 100 mg Agomelatine L(+)-Tartaric acid Alniditan (S-20098 L(+)-Tartaric acid) Cat. No.: HY-17038B (Alnitidan) Cat. No.: HY-101698 Bioactivity: Agomelatine (L(+)-Tartaric acid) is a antidepressant, which is Bioactivity: Alniditan is a potent 5-HT1B/1D receptors agonist, with classified as a norepinephrine-dopamine disinhibitor (NDDI) IC of 1.7 and 1.3 nM in HEK293 cells, and pK value of 8.96 due to its antagonism of the 5-HT2C receptor. 50 i and 9.40 for 5-HT 1B/1D receptors, respectively. Purity: >98% Purity: >98% Clinical Data: Launched Clinical Data: No Development Reported Size: 10mM x 1mL in DMSO, Size: 1 mg, 5 mg, 10 mg, 20 mg 5 mg, 10 mg, 50 mg, 100 mg www.MedChemExpress.com 5 Alosetron Alosetron ((Z)-2-butenedioate) (GR 68755 (GR 68755; GR 68755X) Cat. No.: HY-70050A ((Z)-2-butenedioate); GR 68755X ((Z)-2-butenedioate)) Cat. No.: HY-70050B Bioactivity: Alosetron (GR 68755) is a Serotonin 5HT3-receptor antagonist Bioactivity: Alosetron (Z)-2-butenedioate (GR 68755 (Z)-2-butenedioate) is that is used in treatment of irritable bowel syndrome. IC50 a Serotonin 5HT3-receptor antagonist that is used in treatment Value: Target: 5-HT Receptor Alosetron has an antagonist of irritable bowel syndrome.
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