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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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
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 >
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Akt AMPK ATM/ATR DNA-PK GSK-3 MELK mTOR PDK-1 PI3K PI4K PIKfyve PTEN
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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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Maropitant

Maropitant is a neurokinin (NK1) receptor antagonist. IC50 value:Target: NK1 receptorMaropitant is the first NK1 receptor antagonist developed to treat and prevent emesis in dogs. Treatment with 1 mg/kg Maropitant citrate, significantly reduced the size of ulcerative dermatitis (UD) lesions in mice. Intravenous Maropitant decreased (p < 0.05) MAC by 16% (1.74 ± 0.17%). In contrast, epidural administration of either saline or Maropitant did not change (p > 0.05) the MAC (2.17 ± 0.34% and 1.92 ± 0.12%, respectively).

  • CAS Number: 147116-67-4
  • MF: C32H40N2O
  • MW: 468.67300
  • Catalog: Neurokinin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

UBP141

UBP141 is a GluN2C/2D (NR2C/2D)-preferring receptor antagonist, with Kds of 2.8, 4.2, 14.2, and 19.3 μM for NMDA receptor subtypes: GluN2C, 2D, 2A, and 2B, respectively. UBP141 can induce potent motor impairment in WT mice[1][2].

  • CAS Number: 344768-30-5
  • MF: C21H18N2O5
  • MW: 378.38
  • Catalog: iGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

6-HYDROXYDOPAMINE HYDROBROMIDE

Oxidopamine hydrobromide is a selective catecholaminergic neurotoxin, depletes brain catecholamine levels via uptake and accumulation by a transport mechanism specific to these neurons. In vitro: Oxidopamine hydrobromide-induced apoptosis of PC12 cells was initiated by superoxide generation followed by caspase cascade activation, which was associated with the suppressed Akt phosphorylation and increased p38 phosphorylation. It is likely that pCPT-cAMP prevented the Oxidopamine hydrobromide-induced apoptosis via activation of the PI3-kinase/Akt pathway without any effect on superoxide generation or mitochondrial membrane depolarization. [1]In vivo the presence of sulfhydryl antioxidants protected against neuronal degeneration in the striatum, which was particularly remarkable in the case of CySH and was attributed to its capacity to remove the H2O2 produced in the autoxidation of Oxidopamine hydrobromide.

  • CAS Number: 636-00-0
  • MF: C8H12BrNO3
  • MW: 250.090
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: 406ºC at 760 mmHg
  • Melting Point: 216-220 °C(lit.)
  • Flash Point: 199.3ºC

Decamethonium Bromide

Decamethonium Bromide is a nicotinic AChR partial agonist and neuromuscular blocking agent.Target: nAChRDecamethonium (Syncurine) is a depolarizing muscle relaxant or neuromuscular blocking agent, and is used in anesthesia to induce paralysis. Decamethonium, which has a short action time, is similar to acetylcholine and acts as a partial agonist of the nicotinic acetylcholine receptor. In the motor endplate, it causes depolarization, preventing further effects to the normal release of acetylcholine from the presynaptic terminal, and therefore preventing the neural stimulus from affecting the muscle. In the process of binding, decamethonium actually activates (depolarizes) the motor endplate, but since the decamethonium itself is not degraded, the membrane remains depolarized and unresponsive to normal acetylcholine release [1].

  • CAS Number: 541-22-0
  • MF: C16H38Br2N2
  • MW: 418.294
  • Catalog: nAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 263-267 °C(lit.)
  • Flash Point: N/A

RS 127445

RS 127445 is a novel high affinity, selective 5-HT2B receptor antagonist with pKi of 9.5.

  • CAS Number: 199864-86-3
  • MF: C17H17ClFN3
  • MW: 317.78800
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

LY-281217

LY-281217 is a potent mu-opioid agonist with analgesic effects[1].

  • CAS Number: 105027-75-6
  • MF: C32H42N4O6
  • MW: 578.69900
  • Catalog: Opioid Receptor
  • Density: 1.199g/cm3
  • Boiling Point: 786.4ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 429.4ºC

4,4'-((2beta,3alpha,5alpha,16beta,17beta)-3,17-Bis(acetyloxy)androstane-2,16-diyl)bis(1,1-dimethyl-piperazinium) dibromide

Pipecuronium bromide is a potent long-acting nondepolarizing steroidal neuromuscular blocking agent (NMBA), and a bisquaternary ammonium compound. Pipecuronium bromide is a powerful competitive nAChR antagonist with a Kd of 3.06 μM[1][2][3][4][5].

  • CAS Number: 52212-02-9
  • MF: C35H62Br2N4O4
  • MW: 762.69900
  • Catalog: nAChR
  • Density: 1.329
  • Boiling Point: N/A
  • Melting Point: 262-264ºC
  • Flash Point: N/A

Caroverine HCl

Caroverine hydrochloride is a potent, competitive and reversible antagonist of NMDA and AMPA glutamate receptor. Caroverine hydrochloride is also an antioxidant and calcium-blocking agent that exhibits vasorelaxant action. Caroverine hydrochloride can be used for the research of inner ear tinnitus[1][2][3].

  • CAS Number: 55750-05-5
  • MF: C22H28ClN3O2
  • MW: 401.93000
  • Catalog: iGluR
  • Density: 1.11g/cm3
  • Boiling Point: 521.2ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 269ºC

Cyamemazine

Cyamemazine is a neuroleptic agent that contains the phenothiazine chromophore. Cyamemazine is often used as an anxiolytic. Cyamemazine is a potent 5-HT3 (Ki of 12 nM), 5-HT2A (Ki = 1.5 nM) and 5-HT2C (Ki of 75 nM) receptors antagonist with antipsychotic activity[1][2].

  • CAS Number: 3546-03-0
  • MF: C19H21N3S
  • MW: 323.455
  • Catalog: 5-HT Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 479.0±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 243.5±28.7 °C

Salfaprodil

Salfaprodil (Neu2000 potassium) is an NR2B-selective and uncompetitive antagonist of N-methyl-D-aspartate (NMDA), and a free radical scavenger. Salfaprodil has excellent neuroprotection against NMDA- and free radical-induced cell death[1][2].

  • CAS Number: 916214-57-8
  • MF: C15H7F7KNO3
  • MW: 421.31
  • Catalog: iGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PAP

Phenthoate is an organophosphorus pesticide having low toxicity in animals. Phenthoate is also a AChE inhibitor[1][2].

  • CAS Number: 2597-03-7
  • MF: C12H17O4PS2
  • MW: 320.365
  • Catalog: AChE
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 379.5±52.0 °C at 760 mmHg
  • Melting Point: 156ºC
  • Flash Point: 183.3±30.7 °C

Clorgyline hydrochloride

Clorgyline hydrochloride is an irreversible and selective inhibitor of monoamine oxidase A (MAO-A) that is used in scientific research; structurally related to Pargyline.

  • CAS Number: 17780-75-5
  • MF: C13H16Cl3NO
  • MW: 308.631
  • Catalog: Monoamine Oxidase
  • Density: N/A
  • Boiling Point: 361.3ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 172.3ºC

Isomeranzin

Isomerazin is a coumarin isolated from Poncirus trifoliate Raf., and shows cholinesterase inhibition[1][2].

  • CAS Number: 1088-17-1
  • MF: C15H16O4
  • MW: 260.285
  • Catalog: AChE
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 423.4±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 188.9±28.8 °C

Ajmalicine

Ajmalicine (Raubasine) is found in herbs of Catharanthus roseus, is an antihypertensive drug used in the treatment of high blood pressure, decreases peripheral resistance and blood pressure[1].Ajmalicine (Raubasine) is an adrenolytic drug which preferentially blocks alpha 1-adrenoceptor than alpha 2-adrenoceptor[2].Ajmalicine (Raubasine) is an reversible non-competitive nicotine receptor antagonist with an IC50 of 72.3 μM[3].Ajmalicine (Raubasine) acts preferentially at postsynaptic sites, competitively antagonizes the effect of noradrenaline on postsynaptic alpha-adrenoceptor with a pA2 value of 6.57, blocks the inhibitory effect of clonidine with an pA2 value of 6.2[4].

  • CAS Number: 483-04-5
  • MF: C21H24N2O3
  • MW: 352.427
  • Catalog: Adrenergic Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 524.0±50.0 °C at 760 mmHg
  • Melting Point: 258°C (rough estimate)
  • Flash Point: 270.7±30.1 °C

NMDAR/TRPM4-IN-2

NMDAR/TRPM4-IN-2 (compound 8) is a potent NMDAR/TRPM4 interaction interface inhibitor. NMDAR/TRPM4-IN-2 shows neuroprotective activity. NMDAR/TRPM4-IN-2 prevents NMDA-induced cell death and mitochondrial dysfunction in hippocampal neurons, with an IC50 of 2.1 μM. NMDAR/TRPM4-IN-2 protects mice from MCAO-induced brain damage and NMDA-induced retinal ganglion cell loss[1].

  • CAS Number: 2243506-33-2
  • MF: C11H19BrCl2N2
  • MW: 330.09
  • Catalog: ERK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Vazegepant

Vazegepant is the first intranasal CGRP receptor antagonist for the study the acute research of migraine[1][2].

  • CAS Number: 1337918-83-8
  • MF: C36H46N8O3
  • MW: 638.80
  • Catalog: CGRP Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 933.7±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 518.5±34.3 °C

Methyl tridecanoate-d25

Methyl tridecanoate-d25 is the deuterium labeled Methyl tridecanoate. Methyl tridecanoate moderately inhibits β-amyloid aggregation. Methyl tridecanoate weakly inhibits acetylcholinesterase (AChE)[1].

  • CAS Number: 1219804-90-6
  • MF: C14H3D25O2
  • MW: 253.52
  • Catalog: AChE
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SB-277011 hydrochloride

SB-277011 hydrochloride (SB-277011A hydrochloride) is a potent, selective, orally bioavailable and brain penetrate dopamine D3 receptor (D3R) antagonist with Ki values of 10.7 nM and 11.2 nM at rodent and human D3R, respectively. SB-277011 hydrochloride displays 80- to 100-fold selectivity over other dopamine receptors with pKis of 8.0, 6.0, <5.2, and 5.9 for D3, D2, 5-HT1B, and 5-HT1D receptors, respectively[1][2].

  • CAS Number: 215804-67-4
  • MF: C28H31ClN4O
  • MW: 438.564
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Oxidopamine hydrochloride

Oxidopamine hydrochloride is a neurotoxic synthetic organic compound, selectively destroys dopaminergic and noradrenergic neurons in the brain.

  • CAS Number: 28094-15-7
  • MF: C8H12ClNO3
  • MW: 205.63900
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: 406ºC at 760 mmHg
  • Melting Point: 232-233ºC (dec.)(lit.)
  • Flash Point: 199.3ºC

LY 235959

LY 235959 is a competitive N-methyl-D-aspartate (NMDA)-receptor antagonist. LY 235959 potentiates the anticonvulsant action of antiepileptics[1].

  • CAS Number: 137433-06-8
  • MF: C11H20NO5P
  • MW: 277.25400
  • Catalog: iGluR
  • Density: 1.339g/cm3
  • Boiling Point: 539.6ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 280.1ºC

DREADD Agonist 21

DREADD agonist 21 is a potent human muscarinic acetylcholine M3 receptors (hM3Dq) agonist(EC50=1.7 nM).

  • CAS Number: 56296-18-5
  • MF: C17H18N4
  • MW: 278.352
  • Catalog: mAChR
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 470.1±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 238.1±31.5 °C

Iptakalim hydrochloride

Iptakalim hydrochloride, a lipophilic para-amino compound, is a novel ATP-sensitive potassium channel (KATP) opener, as well as an α4β2-containing nicotinic acetylcholine receptor (nAChR) antagonist[1].

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

PHACLOFEN

Phaclofen is a selective GABAB receptor antagonist. Phaclofen is a peripheral and central baclofen antagonist. Phaclofen maybe a potential compound in determining the physiological significance of central and peripheral bicuculline-insensitive receptors with which GABA and (-)-baclofen interact[1][2].

  • CAS Number: 114012-12-3
  • MF: C9H13ClNO3P
  • MW: 249.63100
  • Catalog: GABA Receptor
  • Density: 1.432 g/cm3
  • Boiling Point: 467.1ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 236.3ºC

Tat-NR2Baa

Tat-NR2BAA is the control peptide of Tat-NR2B9c (HY-P0117), inactive. The sequence of Tat-NR2BAA is similar to Tat-NR2B9c, but it has a double-point mutation in the COOH terminal tSXV motif, making it incapable of binding PSD-95. Tat-NR2B9c is a membrane-permeant peptide and disrupts PSD-95/NMDAR binding, correlate with uncoupling NR2B- and/or NR2A-type NMDARs from PSD-95[1][2].

  • CAS Number: 847829-41-8
  • MF: C103H184N42O29
  • MW: 2474.83
  • Catalog: NO Synthase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

acephate

Acephate is an anticholinesterase insecticide that produces cholinotoxicity. Acephate displays weak inhibition of rat AChE but potently inhibits cockroach AChE.

  • CAS Number: 30560-19-1
  • MF: C4H10NO3PS
  • MW: 183.166
  • Catalog: AChE
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 2ºC
  • Melting Point: 93°C
  • Flash Point: 2 °C

Flufiprole

Flufiprole is a nonsystemic phenylpyrazole insecticide targeting the GABA receptor used in the rice field. Flufiprole is excellent in controlling a wide range of pests[1].

  • CAS Number: 704886-18-0
  • MF: C16H10Cl2F6N4OS
  • MW: 491.23800
  • Catalog: GABA Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SCH 221510

SCH 221510 is a potent, orally active and selective NOP (nociceptin opioid receptor) agonist, with an EC50 of 12 nM and Ki of 0.3 nM. SCH 221510 shows an anxiolytic-like effect[1].

  • CAS Number: 322473-89-2
  • MF: C28H31NO
  • MW: 397.55
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(4R,4aS,7aR,12bS)-3-(cyclopropylmethyl)-4a,7,9-trihydroxy-N-[2-(3-phenyl-1,2,4-oxadiazol-5-yl)propan-2-yl]-1,2,4,5,7a,13-hexahydro-4,12-methanobenzofuro[3,2-e]isoquinoline-6-carboxamide,4-methylbenzenesulfonic acid

Naldemedine (S-297995) tosylate is an orally active μ-opioid receptor antagonist (PAMORA)[1]. Naldemedine tosylate shows potent binding affinities (Ki=0.34, 0.43, 0.94 nM, respectively) and antagonist activities (IC50=25.57, 7.09, 16.1 nM, respectively) for recombinant human μ-, δ-, and κ- opioid receptors[2]. Naldemedine can be used in opioid-induced constipation (OIC) research[2]. Naldemedine tosylate is predicted to bind to 3CLpro encoded by SARS-CoV2 genome[3].

  • CAS Number: 1345728-04-2
  • MF: C39H42N4O9S
  • MW: 742.83700
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Talnetant

Talnetant (SB 223412) is a potent and selective NK3 receptor antagonist (ki=1.4 nM, hNK-3-CHO); 100-fold selective for the hNK-3 versus hNK-2 receptor, with no affinity for the hNK-1 at concentrations up to 100 uM.IC50 Value: 1.4 nM (hNK-3-CHO binding Ki) [1]Target: NK3 receptorin vitro: In vitro studies demonstrated that 53 is a potent functional antagonist of the hNK-3 receptor (reversal of senktide-induced contractions in rabbit isolated iris sphincter muscles and reversal of NKB-induced Ca2+ mobilization in CHO cells stably expressing the hNK-3 receptor), while in vivo this compound showed oral and intravenous activity in NK-3 receptor-driven models (senktide-induced behavioral responses in mice and senktide-induced miosis in rabbits) [1]. Talnetant has high affinity for recombinant human NK3 receptors (pKi 8.7) and demonstrates selectivity over other neurokinin receptors (pKi NK2 = 6.6 and NK1<4). In native tissue-binding studies, talnetant displayed high affinity for the guinea pig NK3 receptor (pKi 8.5) [3].in vivo: Rectal barostat tests were performed on 102 healthy volunteers, randomized to receive either oral talnetant 25 or 100 mg or placebo over 14-17 days [2]. Talnetant (3-30 mg/kg i.p.) significantly attenuated senktide-induced 'wet dog shake' behaviors in the guinea pig in a dose-dependent manner. Microdialysis studies demonstrated that acute administration of talnetant (30 mg/kg i.p.) produced significant increases in extracellular dopamine and norepinephrine in the medial prefrontal cortex and attenuated haloperidol-induced increases in nucleus accumbens dopamine levels in the freely moving guinea pigs [3].Toxicity: Talnetant had no effect on rectal compliance, sensory thresholds or intensity ratings compared with placebo [2].Clinical trial: Study Of Talnetant Versus Placebo And Risperidone In Schizophrenia. Phase 2

  • CAS Number: 174636-32-9
  • MF: C25H22N2O2
  • MW: 382.45400
  • Catalog: Neurokinin Receptor
  • Density: 1.212g/cm3
  • Boiling Point: 580.4ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 304.8ºC

tribendimidine

Tribendimidine is an orally active, broad-spectrum anthelmintic agent, with particularly high activity against A. lumbricoides and N. americanus. Tribendimidine is also an L-type nicotinic acetylcholine receptor (nAChR) agonist[1][2][3].

  • CAS Number: 115103-15-6
  • MF: C28H32N6
  • MW: 452.59400
  • Catalog: nAChR
  • Density: 1.04g/cm3
  • Boiling Point: 618.2ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 327.7ºC