MCE 神经科学产品 Neuroscience Product

www.MedChemE

MedChemExpress

Neuroscience

ProductHandbook

Pain

Biological

Rhythms

andSleep

Neuromuscular

Diseases

Somatosensation

metabolism

AutonomicNeuroendocrine

Regulation

Processes

transduction

Behavioral

Neuroethology

Fromtheitinerariesof

featuresoding

FoodIntake

Neuroendocrinoralandspeech

andEnergyBalance

vocal/social

8,329attendees

Touch

Development

Thirstand

communication

atthe2018SfNmeeting

IonChannels

WaterBalance

Stressand

socialbehavior

andEvolution

peptides

socialcognition

opiates

theBrain

monoamines

SpinalCord

Adolescent

autismDevelopmentalDevelopment

PTSD

InjuryandPlasticity

Postnatal

fear

humansocial

Neurogenesis

Disorders

Mood

Human

ADHD,

Disorders

Anxiety

cognition

Neurogenesis

dystexia

depression

Appetitive

Cognitionand

timing

Behavior

andGllogenesis

bipolar

andAversive

DevelopmentofMotor,

Schizophrenia

perception

Learning

Sensory,andLimbicSystems

executive

attention

perceptuallearning

human

Parkinson's

GlialMechanisms

StemCells...

mitochondria

OtherPsychiatricEmotionfunction

biomarkers

reinforcement

long-term

Disease

Huntington's

Transplant

Synaptogenesis

Motivation

human

human

memory

Axonand

and...DevelopmentNeurotransm.,

decisions

working

andRegen

Transportors,

memory

animal

OtherMovement

PNS

Dendrite

G-Protein...Signaling

reward

decision

visual

model

microgliaDemyelinating

Development

Receptors

dopamine

making

decisionslearningandmemory

Disorders

NMDA

ataxia

Disorders

GABA,

LTP

Synaptic

placecells,

striatum

gridcells

Neuro-Oncology

gly...

Plasticity

Biomarkerand

Epilepsy

K

executive

hippocampus

Neuroimmunology

CaGlu

Trans

BasalGanglia

DrugDiscovery

degene

function

Neurotoxicity,

mission

Animal

Alzheimer'sDiseaseration

Ligand-Gated

attention

Inflammation...

Channels

Release

Cognitionand

andotherDementia

Ischemia

thalamus,brainstem

motecular

Behavior

protection

Membrane

Netword

Down

Stroke

human

mechanisms

BrainWellness

nicotinic

Properties

interactions

Brain

language

andAging

Injuryand

Physiological

oscillations

auditory

Auditory&

Trauma

Vestibular

plasticityAnatomical

tools

Systems

BrainBloodFlow,

thalamus,

optical

DataAnalysis

Vis.&Aud.

retina

memory.aging

Metabolism,Homeostasis

barrels

e-phys

andStats

Disorders

visualcortex

Tauopathies,

haircells

faces,

Tau-dementias,

humancognitive

Molecular,Biochemical,

Computation,

EyeMovements

andPriondiseases

Modeling,

vestibular

objests

aging

GeneticTechs

Simulation

eye

Vision

dystonia

SystemsBiology

Brain-Machine

Multisensory

move

clinicaltrials

vis.attention

andBioinformatics

Interface

Integration

OtherMovement

Oifaction

VisualSensory-

Disorders

andTaste

Cerebellum

motorProcessing

reaching:motorleaming

MotorNeurons

visualreaching

andMuscle

Development

NeuralExcitability,Synapses,andGlia

NeurodegenerativeDisordersandInjury

SensorySystems

MotorSystems

IntegrativePhysiologyandBehavior

MotivationandEmotion

Cognition

I.Techniques

Respiratory

reachingcontrol

DrugsofAbuse

Regulation

andAddiction

Voluntary

Movements

RhythmicMotor

Posture

PatternGeneration

andGait

EachdotisaTopicDotsizeindicatespopularity

Analysis:MatteoCarandini

Date:SocietyforNeuroscience

Reference:Carandini,M.,ChartingtheStructureofNeuroscience.Neuron,2019.102(4):p.732-734.

MCE

MasterofBioactiveMolecules

Neuroscience

Introduction

Neuroscienceisthemostfascinatingdisciplinethatattemptstounderstandthenervoussystemandtodeveloppotentialtherapies.Therearesomanybranchesofneuroscience,amongwhichdevelopment,neuralsignaling,neurodegenerativedisorders,sensory/motorsystem,integrativeneuroscience,motivationandemotion,cognitionandtechniquesarementionedwithhighfrequencies.

Inthishandbook,neurotransmittersandtheirreceptors,neuronalstemcells,neurodegenerativediseases,blood-brainbarrierwillbediscussed.

Contents

NeurotransmittersandNeurotransmitterReceptors

2

NeuralStemCells

5

NeurodegenerativeDiseases

8

BloodBrainBarrier

10

NeurotransmittersandNeurotransmitterReceptors

Neurotransmittersarethesmallmoleculesofchemicalsubstancesthatcarryinformationbetweenneurons.Thereareseveraltypesofneurotransmittersaccordingtochemicalproperties,includingmonoaminesandacetylcholine,aminoacids,purines,lipidsandpeptides.

Neurotransmittersinducepostsynapticelectricalpotentialsandbiochemicalchangesthroughtheirreceptors.Themostfamiliarneurotransmitterreceptorsareligand-gatedchannelsandGprotein-coupledreceptors(GPCRs)(Figure1).Whenaligand(neurotransmitter)bindstotheextracellulardomain,theligand-gatedchannelswillopenacentral

Ligand-gatedionchannel

Gprotein-coupledreceptor

Neurotransmitter

Receptor

Neurotransmitter

Channel

Effector

Extracellularside

Gate

function

Second

Gate

messenger

γ

generating

Cytoplasmicside

enzyme

α

β

P

Receptor

GDP

Gprotein

γ

α

β

Second

Protein

messenger

kinase

GTP

Figure1.Neurotransmitterreceptors[1]

porethatpermitsionstopasswhileGPCRswilltransmitthesignaltoactivateGproteinsandthenamplifythesignalingcascadesthroughsecondmessengers.

2

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Inhibitors • ScreeningLibraries • Proteins

Forthecentralroleofneurotransmitters,neurotransmitterreceptorsarecriticaltargetsforthetreatmentofnervoussystemrelateddiseasessuchaspsychiatricandneurologicdisorders.

Compounds

Cat.No.

ProductName

Description

HY-B0282

Acetylcholinechloride

Acommonneurotransmitterfoundinthecentralandperipheral

nervesystem.

HY-106094

CY208-243

AselectivedopamineD1receptoragonistwhichexhibits

anti-parkinsonianactivity.

HY-B1473

Serotoninhydrochloride

AmonoamineneurotransmitterintheCNSandanendogenous5-HT

receptoragonist.

HY-B1204

Histamine

Anorganicnitrogenouscompoundinvolvedinlocalimmune

responsesandactsasaneurotransmitter.

HY-N0067

γ-Aminobutyricacid

Amajorinhibitoryneurotransmitterintheadultmammalianbrain,

bindstoGABAreceptors.

HY-14608

L-Glutamicacid

Actsasanexcitatorytransmitterandanagonistatallsubtypesof

glutamatereceptors.

HY-P0288

Leu5-Enkephalin

Apentapeptidewithmorphinelikeproperties.Actsasanagonistat

opioidreceptors.

HY-P1866

β-Endorphin,equine

Anendogenousopioidpeptidethatbindstobothμ/δopioid

receptors.Analgesicproperties.

HY-P0201

SubstanceP

Aneuropeptide,actingasaneurotransmitterandasa

neuromodulatorintheCNS.

HY-P1480

NeuropeptideY

AneuropeptideYreceptoragonist.

HY-P1339

OrexinB,human

Anendogenousagonistoforexinreceptor.

HY-P0049

Argipressin

AnendogenoushormonebindstotheV1,V2,V3-vasculararginine

vasopressinreceptor.

HY-17571

Oxytocin

Amammalianneurohypophysialhormone.

HY-P0015

Somatostatin

Atetradecapeptidewhichcancontrolgrowthhormoneandpituitary

hormonesecretioninCNS.

HY-P0234

Neurotensin

Aguttridecapeptidethatpossesseshigh-affinityneurotensin

receptors(NTR).

3

MCE

MasterofBioactiveMolecules

Cat.No.

ProductName

Description

HY-P0195

Bombesin

Atetradecapeptidethatplaysanimportantroleinthereleaseof

gastrinandtheactivationofG-proteinreceptors.

HY-P1765

Galanin(1-19),human

Awidelydistributedneuropeptidewithdiversebiologicaleffects.

HY-B0495

Lamotrigine

Ananti-convulsantthatinhibitsvoltage-sensitivesodium

channels.

HY-P1317A

Nociceptin(1-13),amide

ApotentORL1receptor(opioidreceptor-like1receptor,OP4)

agonist.

HY-12987

Pimozide

Adopaminereceptorantagonist.

HY-15399

Vigabatrin

AninhibitoryneurotransmitterGABAvinyl-derivative,isanorally

activeandirreversibleGABAtransaminaseinhibitor.

HY-12152

PNU-120596

Aselectiveα7nAChRpositiveallostericmodulatorforpsychiatric

andneurologicaldisordersresearch.

HY-14418

VU0361737

ACNSpenetrantpositiveallostericmodulatorofmetabotropic

glutamatereceptor4(mGluR4PAM).Neuroprotectiveeffect.

HY-B0527A

Amitriptyline

Aninhibitorofserotoninreuptaketransporterandnoradrenaline

reuptaketransporter.Antidepressantactivity.

HY-15430A

Encenicline

Apartialagonistofα7neuronalnicotinicacetylcholinereceptors

(nAChRs).

HY-15608

MPTP

Abrainpenetrantdopamineneurotoxin,inducingParkinson’s

Disease.

HY-136390

ML417

AselectiveandbrainpenetrantD3dopaminereceptor(D3R)

agonistandexhibitsneuroprotection.

HY-19918A

Anatabine

Atobaccoalkaloidthatcancrosstheblood-brainbarrier.Apotent

α4β2nAChRagonistforneurodegenerativedisorderstreatment.

CompoundScreeningLibraries

Cat.No.:HY-L062

NeurotransmitterReceptorCompoundLibrary

Auniquecollectionofcompoundstargetingavarietyofneurotransmitterreceptors.

Cat.No.:HY-L006

GPCR/GProteinCompoundLibrary

AuniquecollectionofcompoundstargetingGPCRsforvariousGPCRs-relatedresearchanddrugdevelopmentprojects.

4

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Inhibitors • ScreeningLibraries • Proteins

NeuralStemCells

Neuralstemcells(NSCs)havetheabilitytoself-renewandtodifferentiateintothreeneurallineages(i.e.neurons,oligodendrocytesandastrocytes).So,NSCsare

promisingtherapeuticsfordiseasesassociatedwiththenervoussystem.

Exceptfordirectisolationfromprimarytissues,NSCscanalsobeobtainedbydifferentiationfrompluripotentstemcellsandtransdifferentiationfromsomaticcells.Nowadays,smallmoleculesarereportedtogaintheirrolesintransdifferentiatingsomaticcellsintoNSCsandsomeofthemarelistedasfollowed.

However,itisalsoimportanttomaintainthebalancebetweentheproliferationanddifferentiationofNSCsasaberrantNSCproliferationcanleadtotumorigenesis.

Cellreplacement

Neuralprotection

Neuron

Neuronalprogenitor

Solublefactors

Neural

stemcell

Astrocyte

Glialprogenitor

Oligodendrocyte

Figure2.FunctionsofNSCs[2]

Compounds

Cat.No.

ProductName

Description

HY-15036

Diclofenac

ActsasaCOXinhibitorandinducesapoptosisofneuralstemcells(NSCs).

HY-12323

ISX-9

Apotentinducerofadultneuralstemcelldifferentiation.

HY-10585

Valproicacid(VPA)

ApotentHDACinhibitorforthetreatmentofepilepsy,bipolar

disorderandpreventionofmigraineheadaches.

HY-10182

Laduviglusib(CHIR99021)

ApotentandselectiveGSK-3α/βinhibitor,enhancesmouseand

humanembryonicstemcellsself-renewal.

HY-13012

Repsox

ApotentandselectiveoftheTGFβR-1/ALK5inhibitor.RepSoxcan

replaceSox2.

HY-10432

A83-01

ApotentinhibitorofTGF-βtypeIreceptorALK5kinase,typeInodal

receptorALK4andtypeInodalreceptorALK7.

HY-10587

BIX-01294

AninhibitorofG9ahistonemethyltransferase.

HY-13642

RG108

Anon-nucleosideDNAmethyltransferasesinhibitor.

HY-B0166

VitaminC

Anelectrondonorandanendogenousantioxidantagent.

HY-10254

Mirdametinib

Anorallyactive,selectiveandMEKinhibitor.

5

MCE

MasterofBioactiveMolecules

Cat.No.

ProductName

Description

HY-14649

Retinoicacid

AnaturalagonistofRARnuclearreceptors.Playsimportantrolesin

cellgrowth,differentiation,andorganogenesis.

HY-12071

LDN193189

AselectiveBMPtypeIreceptorinhibitor.

HY-124899

Hh-Ag1.5

ApotentHedgehogagonistthatbreaksthequiescenceof

non-injuredliverstemcellsforrescuingliverfailure.

HY-B1496

Tranylcyprominehemisulfate

AnirreversibleMAOinhibitorforthetreatmentofdepression.

HY-100200

SMER28

ApositiveregulatorofautophagyinanmTOR-independentmanner.

PreventstheaccumulationofAβpeptide.

HY-13257

Thiazovivin

AROCKinhibitorthatprotectshumanembryonicstemcells.

ImprovestheefficiencyofiPSCgeneration.

HY-15108

Purmorphamine

Asmoothened(Smo)receptoragonistthatstimulatesosteogenic

differentiationinmurineandhumancells.

HY-10591

Neuropathiazol

Inducesneuronaldifferentiationofmultipotenthippocampalneural

progenitorcells.

HY-103361

SB297006

ACCR3antagonistthatsignificantlyinhibitsproliferationand

neurosphereformationinCCL11-treatedneuralprogenitorcells.

HY-108439

Neurodazine

Apromoterofneurogenesisinpluripotentcells.Promotes

neurogenesisbyactivatingWntandShhsignalingpathways.

HY-W019870

Glufosinate

Aphosphinicacidanalogueofglutamicacid,whichexerts

neurotoxicactivity.

HY-N6953

GarcinoneD

AnaturalxanthonethatpromotestheproliferationofC17.2neural

stemcell.

HY-10046

Plerixafor

AselectiveCXCR4antagonist.Ahematopoieticstemcell(HSC)

mobilizer.

HY-15838

ID-8

ADYRKinhibitorthatsustainsembryonicstemcell(ESC)

self-renewalandpluripotency.

HY-10936

S18986

Aselective,orallyactive,brainpenetrantAMPApositiveallosteric

modulatorthatenhancescognitiveproperties.

HY-108628

SU16f

AselectivePDGFRβinhibitorthatblocksthepromotingroleof

GC-MSCsingastriccancercellproliferationandmigration.

HY-N0204

PulchinenosideA

Anaturaltriterpenoidsaponin.AMPARandNMDARmodulator.

6

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Inhibitors • ScreeningLibraries • Proteins

CompoundScreeningLibrary

Cat.No.:HY-L039

ReprogrammingCompoundLibrary

Auniquecollectionofcompoundsthatactonreprogrammingsignalingpathways.

ChemicalCocktails

HY-10585

HY-10182

HY-13012

Valproicacid

CHIR99021

RepSox

Acombinationofsmallmoleculesthatinducesreprogrammingofmousefibroblastsandhumanurinarycellsintoneuralprogenitorcell[3].

HY-10585

HY-10182

HY-10432

HY-10587

HY-13642

Valproicacid

CHIR99021

A83-01

BIX-01294

RG108

HY-B0166

HY-10254

VitaminC

Mirdametinib

Acombinationofsmallmoleculesthatinducesreprogrammingofmousefibroblastsintoneuralstemcell[4].

HY-10182

HY-10432

HY-124899

HY-100200

HY-12071

CHIR99021

A83-01

Hh-Ag1.5

SMER28

LDN193189

HY-B1496

HY-13642

Tranylcypromine

RG108

Acombinationofsmallmoleculesthatinducesreprogrammingofmousefibroblastsintoneuralstemcell-likecells(ciNSLCs)[5].

HY-10432

HY-13257

HY-15108

HY-10585

A83-01

Thiazovivin

Purmorphamine

Valproicacid

Acombinationofsmallmoleculesthatinducesreprogrammingofmousefibroblastsintoneuralstemcell[6].

HY-10585

HY-10182

HY-12071

HY-10431

HY-15682

Valproicacid

CHIR99021

LDN193189

SB-431542

TTNPB

HY-13257

HY-13027

HY-12848

HY-15108

Thiazovivin

DAPT

SAG

Purmorphamine

Acombinationofsmallmoleculescanreprogramhumanastrocytesintofullyfunctionalneurons[7].

7

MCE

MasterofBioactiveMolecules

NeurodegenerativeDiseases

NeurodegenerativediseasesareaseriesofdiseasescausedbytremendousneuronaldysfunctionanddeathincludingParkinson’sDisease(PD),Alzheimer’sDisease(AD),Huntington’sDisease(HD),AmyotrophicLateralSclerosis(ALS),andPrionDiseases,etc.Itisreportedthatoxidativestress,environmentalfactors,agingandproteindysfunctionarethemajorriskfactorsforneurodegeneration.

Proteinmisfolding,accumulationandaggregationarecommoncharacteristicsinmanyneurodegenerativediseases.Proteinaggregatesformedbyproteinssuchasα-synuclein,tau,and

Health

Neurodegeneration

Misfoledproteins

Lysosomal

Alteredglialfunction

andabnormalprotein

depletion

accumulation

andinflammation

Neuron

Glialcell

Mitochondrial

dysfunction

β-amyloid(Aβ)peptides

willtriggerunfolded

ImpairedRNAhomeostasis

proteinresponse(UPR),

Figure3.Majorriskfactorscontributetoneurodegeneration[8]

ERstress,andautophagy

ofneurons.Thedysfunctionofmitochondrialmayleadtotheinductionofapoptosis.What’smore,thereportsaboutthefunctionofnon-neuronalcells(glia)andneuroinflammationinneurodegenerationaregrowing.

Compounds

Cat.No.

ProductName

Description

HY-115038

ELN484228

Ablockerofα-synucleinwhichisakeyproteininParkinson’s

Disease.

HY-124876

SynuClean-D

Apotentα-synucleinaggregationinhibitorforthetreatmentof

Parkinson’sDisease.

HY-N2099

OnjisaponinB

Acceleratesthedegradationofmutantα-synuclein,andexhibits

potentialtherapeuticeffectsonParkinson’sDiseaseand

Huntington’sDisease.

HY-50882

ELN318463

Anamyloidprecursorprotein(APP)selectiveγ-secretaseinhibitor.

HY-W010041

Scyllo-Inositol

AnamyloidinhibitorthatlowersamyloidplaquesinanAlzheimer's

Diseasemousemodel.

HY-103374

Phenserine

AnAChEinhibitorthatinhibitsβ-amyloidpeptideformation.

Improvescognitiveperformanceandattenuatestheprogressionof

Alzheimer'sDisease.

8

www.MedChemE

Inhibitors

•ScreeningLibraries

•Proteins

Cat.No.

ProductName

Description

HY-N0064

Macelignan

Possessestherapeuticpotentialsagainstneurodegenerative

diseaseswithoxidativestressandneuroinflammation.

HY-101860

GIBH-130

Aneffectiveinhibitorofneuroinflammationandsignificantly

suppressestheIL-1βsecretionbyactivatingmicroglia.

HY-125999

EPI-589

Aquinonederivative,whichhasthepotentialforthetreatmentof

amyotrophiclateralsclerosis(ALS).

HY-122607

DPA-714

Evaluatesforthespecificimagingofinflammationinvariousmodels

ofneuroinflammationandinabraintumormodel.

HY-135749

BN201

Activatespathwaysassociatedwiththeresponsetostressand

neuronsurvival.Neuroprotectiveeffects.

HY-124293

AA147

Anendoplasmicreticulum(ER)proteostasisregulator.

HY-15976

P7C3

AnorallyavailableandCNSpenetrantaminopropylcarbazole,with

neuroprotectiveeffects.

HY-P1061A

ColivelinTFA

Abrainpenetrantneuroprotectivepeptidethathasthepotentialfor

thetreatmentofAlzheimer'sDiseaseandischemicbraininjury.

HY-17646

Verdiperstat

Aselective,irreversibleandorallyactiveMPOinhibitorthatcanbe

usedintheresearchofneurodegenerativebraindisorders.

HY-105285

Piromelatine

AmelatoninMT1/MT2receptoragonistthatpossesses

anti-neurodegenerative,anxiolyticandantidepressantpotentials.

CompoundScreeningLibraries

Cat.No.:HY-L054

Cat.No.:HY-L069

EndoplasmicReticulumStressCompoundLibrary

Anti-Alzheimer’sDiseaseCompoundLibrary

Auniquecollectionofendoplasmicreticulum

Auniquecollectionofcompoundswithanti-Alzheimer’s

stress-relatedcompoundsthatactsausefultoolfor

DiseaseactivitiesortargetingtheuniquetargetsofAD.

researchingERrelateddiseases.

Cat.No.:HY-L070

NeuroprotectiveCompopundLibrary

Auniquecollectionofcompoundswithpotential

neuroprotectiveactivities.

9

MCE

MasterofBioactiveMolecules

BloodBrainBarrier

Theblood-brainbarrier(BBB)protectsthecentralnervoussystem(CNS)fromtheperipheralbloodcirculationandsuppliesthebrainwiththerequirednutrientsfornormalfunction.Itisamulticellularvascularstructurethatmainlycomposedofbrainmicrovascularendothelialcells(ECs),pericytes,astrocytesandthebasementmembrane(Figure4).ECscellscontributetothebarrierpropertybyformingtightjunctions(TJs)andlimitingtranscytosis.Pericytesarecellsthatcovercapillariesandplayimportantrolesintheformation,maturationandmaintenance

ofBBB.AstrocytesparticipateinBBBmaintenanceandion/watertransportbyinteractingwithECsandpericytes.

FortheimportantrolesinmaintainingthehomeostasisofCNS,

ParenchymalBM

Endothelialcell

BBBdisruptionhasbeenfoundinavarietyofneurological

Pericyte

Tightjunctions

disorders.Meanwhile,BBBisalsoanobstacletodeliver

Astrocyticend-feet

EndothelialBM

beneficialdrugstotreatCNSdiseasesorbraintumors,asithas

theleastpermeablecapillariesintheentirebody.Therefore,itis

crucialtodiscoverdrugswhichcanregulatethisbarrierforthe

treatmentofbrain-baseddiseases,suchasAlzheimer’sDisease(AD),

Parkinson’sDisease(PD)andEpilepsy.

Figure4.Schematicofblood-brainbarrier[9]

Compounds&CompoundScreeningLibraries

Cat.No.

ProductName

Description

HY-114426

AT-1002

Atightjunctionregulatorandabsorptionenhancer.

HY-15204

Tonabersat(SB-220453)

Agap-junctionmodulatorthatpreventsinflammatorydamageinthe

centralnervoussystem.

HY-P0139

Gap27

AsyntheticCx43mimeticpeptide.Agapjunctioninhibitor.

HY-10913

Danegaptide(GAP-134)

Anorallyactivegap-junctionmodifierwithanantiarrhythmiceffect.

HY-13779

J-147

ACNSpenetrantneuroprotectiveagentforcognitiveenhancement.

HY-136341

7,8-Dihydroneopterin

Inducescellularapoptosisinastrocytesandneuronsandcanbe

usedintheresearchofneurodegenerativediseases.

HY-107661

ArundicAcid

Anastrocyte-modulatingagent,whichhasthepotentialforstroke

andAlzheimer’sDiseaseresearch.

HY-10052

Aprepitant(MK-0869)

Aneurokinin1receptorantagonist.ApprovedbyFDAforthe

treatmentofchemotherapy-inducednausea.

HY-100740

Lanabecestat(AZD3293)

ACNSpenetratingBACE1inhibitorforthetreatmentofAlzheimer's

Disease.

10

www.MedChemE

Inhibitors

•ScreeningLibraries•

Proteins

Cat.No.

ProductName

Description

HY-104003

S38093

ACNSpenetratingantagonistofH3receptorthatenhances

hippocampalneurogenesis.

HY-108295

Pivagabine(CXB-722)

Ahydrophobic4-aminobutyricacidderivativewithneuromodulatory

activity.

HY-108710

VU0650786

ACNSpenetrantnegativeallostericmodulatorofmGlu3NAM.

HY-114153

PLX5622

Ahighlyselectivebra