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文档简介

www.MedChemE

MedChemExpress

Immunology

ProductHandbook

EarlyNeoplasia

EarlyInfection

PMN

Macrophage

Macrophage

PMN

Th1cell

Tumorcells

Th1cell

Parenchymalcells

Parenchymalcells

MatureTumor

ProtractedInfection

PD-L1

PD-L1

PD-1

PD-1

Macrophage

Exhausted

Exhausted

Th2cell

Th1cell

Th1cell

Reactivenitrogen

PD-L1

PD-L1

species

Interleukin-10

Th2cell

PD-L1

PD-L1

Myeloid-derived

Myeloid-derived

suppressorcells

suppressorcells

Interleukin-10

Reactivenitrogen

Interleukin-10

species

T-regulatory

T-regulatory

TGF-β

cell

Interleukin-10

Apoptotic

Apoptotic

cell

PMN

PMN

Th1cell

PD-L1

PD-L1

Exhausted

Macrophage

TGF-β

PD-L1

Th1cell

Tumorcells

PD-1

PD-L1

Exhausted

Th1cell

PD-L1

PD-L1

Reference:

RichardS.Hotchkiss,M.D.,

andLyleL.Moldawer,Ph.D.

ParallelsbetweenCancer

andInfectiousDisease.

causinghumancoronavirus[3]

Figure1.Structureofrespiratorysyndrome

Lipidbilayer

Membraneglycoprotein(M)

Spikeprotein(S)

RNA

Envelopeglycoprotein(E)

Nucleocapsidprotein

MCE

MasterofBioactiveMolecules

Immunology

Theimmunesystemisanetworkconsistsofmultiplecells,tissues,andorgansthatworktogethertoprotectanorganismfromdiseases.Immunesystemrecognizesselfandnon-self,andrespondstoawidevarietyofpathogen,fromviruses,bacteria,fungi,parasitestocancercells.

Humanhavetwomajorsubsystemofimmunesystem:theinnateimmunesystemandtheadaptiveimmunesystem.Theinnateimmunesystem,thesystemwebornwith,provideapreconfiguredresponsetobroadgroupsofstimuli,andcanrespondquicklyduringearlyonsetofinfection.Theadaptiveimmunesystemonlydevelopedwhenourbodyisexposedtothepathogen,andcanactwithgreatspecificity.

Inabalancedimmunesystem,immunecellsdistinguish“non-self”from“self”,innateimmunityandadaptiveimmunitycollaboratesefficientlytowipeoutinvaders.Whiledisorderedimmunesystemareleadingcausesofmultiplemajordiseases:inactivatedimmunesysteminduceinfectiousdiseasesandcancer,whileoveractiveimmuneresponseledtoautoimmunediseaseslikelupuserythematosus,rheumatoidarthritis.

Inthisbrochure,briefintroductionswillbegiventoSARS-CoV,cancerimmunotherapy,innateimmunity,inflamma-tionandanti-infection.

Contents

SARS-CoV&AntiviralImmunity

2

Immunity&Inflammation

8

CancerImmunotherapy

6

Anti-infection

10

SARS-CoV&AntiviralImmunity

Coronavirusdisease2019(COVID-19)isaninfectiousdiseasewithmajorsymptomsoffeverandpneumonia.COVID-19iscausedbySARScoronavirus2(SARS-CoV-2),whichbelongstocoronavirus(CoV).CoVhavefourmainstructuralproteins:spike(S),membrane(M),envelope(E),andnucleocapsid(N)proteins[1].

AfterprimedbyaproteasecalledTMPRSS2(transmembraneprotease,serine2),theSproteinmediatestheCoVentryintohostcellsbyattachingtoa

cellularreceptornamedACE2,followedbyfusionbetweenvirusandhostcellmembranes[2].GenomereplicationandsubgenomicRNAtranscriptionafterentrycarryonwiththeparticipationofmanynonstructuralproteinssuchasMpro(mainproteaseor3CLpro),PLpro(papain-likeprotease)andRdRp(RNA-dependentRNApolymerase).Thenthestructuralproteinsaretranslated,assembledintomaturevirions,andreleasedviavesiclesbyexocytosis.What’sworthmentioning,thevastreleaseof

cytokines(suchasIL-1β,GM-CSF,IL-6,IL-10)bytheimmunesysteminresponsetosevereinfectionofSARS-CoV-2calledcytokinestormcontributeslargelytothemortalityofCOVID-19.

2

www.MedChemE

Inhibitors • ScreeningLibraries • Proteins

MCEprovide100+smallmoleculeswithpotentialtocureCOVID-19,includingantiviralcompoundstargetingTMPRSS2,Mpro,PLproetc.,anti-inflammatorydrugslikeDexamethasoneandvariousofimmuneregualtors.

Attachment

SARS-CoV-2

andentry

Viralrelease

ACE2

ACE2

receptor

Fusion

Exocytosis

Uncoating

Vesicle

GenomicRNA(positive)

TranslationofORF1a/ORF1b

5’

3’

Golgi

Replication/Translation

3’

5’(Negative)

ERGIC

Replicase

5’

S

5’

3

Assemblyand

5’

E

budding

mRNAs

5’

M

Translation

5’

6

5’

7a/7b

5’

8

5’

N

/9b

RoughER

5’

3’(Positive)

Spikesprotein

Envelopeprotein

Membraneprotein

Nucleocapsid

Figure2.ThelifecycleofSARS-CoV-2inhostcells[3]

Compounds

Cat.No.

ProductName

Description

HY-14648

Dexamethasone

Glucocorticoidreceptoragonist,highlyeffectiveinthecontrolof

severeCOVID-19.

HY-15287

Nelfinavir

PotentandorallybioavailableHIV-1proteaseinhibitor,alsoinhibits

SARS-CoV.

HY-18649A

Galidesivir

Adenosineanalog,activeinvitroagainstMERS-CoV,SARS-CoV,and

SARS-CoV-2.

HY-117043

GRL0617

InhibitorofSARS-CoVpapain-likeprotease/deubiquitinase.

HY-B1123

Auranofin

Thioredoxinreductase(TrxR)inhibitor,exhibitsantiviralactivity

againstSARS-CoV.

HY-90001

Ritonavir

InhibitorofHIVprotease,usedtotreatAIDS.

HY-14588

Lopinavir

PeptidomimeticinhibitoroftheHIV-1protease.

HY-17589A

Chloroquine

Antimalarialandanti-inflammatoryagentwidelyused,showsin

vitroactivityforSARS-CoV-2infection.

3

MCE

MasterofBioactiveMolecules

Compounds

Cat.No.

ProductName

Description

HY-B1370

Hydroxychloroquine

Syntheticantimalarialagent,efficientlyinhibitsSARS-CoV-2

infectioninvitro.

HY-13004

Maraviroc

SelectiveCCR5antagonistwithactivityagainsthumanHIV.

HY-50101

Mavorixafor

CXCR4antagonist,inhibitsthereplicationofT-tropicHIV-1.

HY-125033

EIDD-1931

Nucleosideanalogandbehavesasapotentanti-virusagent.

HY-12559

Alisporivir

Cyclophilininhibitorwithpotentanti-hepatitisCvirusactivity.

HY-P2036A

FSL-1TFA

Bacterial-derivedTLR2/6agonist,enhancesresistanceto

experimentalHSV-2infection.

HY-B0240

Disulfiram

ALDH1inhibitor,inhibitPlprosofMERS-CoVandSARS-CoV.

HY-13986

Merimepodib

IMPDHinhibitorwithbroadspectrumantiviralactivities.

HY-14768

Favipiravir

PotentviralRNApolymeraseinhibitor.

HY-30234A

Clemizolehydrochloride

H1histaminereceptorantagonist,showsantiviralactivity

againstHCV.

HY-13512

Camostatmesylate

Serineproteaseinhibitorforchronicpancreatitis,showsantiviral

activityagainstSARS-CoV-2.

HY-13750

Ebselen

Potentvoltage-dependentcalciumchannel(VDCC)blocker,an

inhibitorofHIV-1capsidCTDdimerization.

HY-B0182

Carmofur

Acidceramidaseinhibitor,inhibitstheSARS-CoV-2main

protease(Mpro).

HY-17026

Gemcitabine

Pyrimidinenucleosideanalogantimetaboliteand

antineoplasticagent.

HY-10586

5-Azacytidine

NucleosideanalogueofcytidinethatspecificallyinhibitsDNA

methylation.

HY-13605

Cytarabine

Nucleosideanalog,hasantiviraleffectsagainstHSV.

HY-P9917

Tocilizumab

Anti-humanIL-6Rneutralizingantibody,effectiveforthestudyof

severeCOVID-19.

HY-P0012A

Aviptadilacetate

Vasoactiveintestinalpolypeptide,potentiallyusedforSARS-CoV-2

causedrespiratoryfailure.

HY-135867D

NHC-diphosphate

Pyrimidineribonucleoside,behavesasapotentanti-virusagent.

4

www.MedChemE

Inhibitors • ScreeningLibraries • Proteins

Compounds

Cat.No.

ProductName

Description

HY-D1270

DirectViolet1

Textiledye,inhibittheinteractionbetweentheSARS-CoV-2spike

proteinandACE2.

HY-15463

Imatinib

Tyrosinekinasesinhibitor,inhibitsSARS-CoVandMERS-CoV.

HY-13433

Thapsigargin

InhibitorofmicrosomalCa2+-ATPase,efficientlyinhibitscoronavirus

replicationindifferentcelltypes.

HY-100229

Aloxistatin

Broad-spectrumcysteineproteaseinhibitor,exhibitsentry-blocking

effectforMERS-CoV.

HY-B0190A

Nafamostatmesylate

Serineproteaseinhibitor,blocksactivationofSARS-CoV-2.

HY-14904A

Umifenovirhydrochloride

Broad-spectrumantiviralcompound,showsasanefficientinhibitor

ofSARS-CoV-2invitro.

HY-14393

Emodin

Anthraquinonederivative,anti-SARS-CoVcompound.

HY-B0260

Methylprednisolone

Syntheticcorticosteroid,improvessevereorcriticalCOVID-19

byactivatingACE2andreducingIL-6levels.

HY-13765

6-Thioguanine

Anti-leukemiaandimmunosuppressantagent,actsasaninhibitorof

SARSandMERScoronavirusPlpros.

HY-17470

Mizoribine

Imidazolenucleoside,inhibitsHCV,SARS-CoV.

HY-17443

Sivelestat

Neutrophilelastaseinhibitor,potentialusedinCOVID-19.

HY-N0191

Andrographolide

NF-κBinhibitor,showsbroadantiviralactivity.

HY-N0360

DihydrotanshinoneI

Naturalcompoundexhibitsentry-blockingeffectforMERS-CoV.

HY-B0372A

Bromhexinehydrochloride

PotentandspecificTMPRSS2proteaseinhibitor,canpreventand

manageSARS-CoV-2infection.

CompoundScreeningLibrary

Cat.No.:HY-L052

Anti-COVID-19CompoundLibrary

Auniquecollectionof1,500+compoundsthatmayhaveanti-COVID-19activity.

5

MCE

MasterofBioactiveMolecules

CancerImmunotherapy

Immunecheckpointsarekeyimmuneregulatorsinmaintainingimmunehomeostasisandpreventingautoimmuni-ty.Throughre-activatingtheproperfunctionofTcells,Immunecheckpointinhibitorsprovedtobeoneofthemostpromisingtherapeuticmethodsforcancertreatment.Inlightofthis,scientistsaretryingtokillcancersbycancerimmunotherapy,whichistocurecancersbyexploitingourimmunesystem.Severalapproacheshavebeenprovedsuccessfultheseyears,includingimmunecheckpointinhibitors,tumormicroenvironmentmodulators[4].

Thetumormicroenvironment(TME)isthecellularenvironmentinwhichthetumorexists,includingsurroundingbloodvessels,theextracellularmatrix(ECM),othernon-malignantcellsandalsosignalingmolecules.Researchershavediscoveredthatgrowthfactorssecretedbystromalcellsandcancerassociatedfibroblasts(CAFs)cannotonlypromotegrowthandsurvivalofmalignantcellsbutalsofunctionasnegativeregulatorsoftheimmuneresponse[5].MoleculesassociatedwithTMEsuchascytokinereceptors,metabolicenzymesarecriticaltargetsincancerimmunotherapy.ThesetargetsincludeRORγt,Chemokinereceptor(CXCR),Sting,IDO,TLR,etc.

MCEprovideshundredsofproductsregardingcancerimmunotherapy,coveringvarioustargetsincludingPD1/P-DL1CTLA-4,STING,IDO,TLR,etc.

Teffectorcells

ExhaustedTcells

PD-1

CTLA-4

mAbs

Target

mAbs

PD-L1

Effector

CD80/86

cytokines&

APC

cytotoxic

granules

TumorcellsTumorcells

Figure3.ImmunecheckpointblockadeforT-cellactivation[4]

Compounds

Cat.No.

ProductName

Description

HY-12885

ADU-S100

STINGactivator,leadstopotentandsystemictumorregression.

HY-10964

Vadimezan

MurineagonistofSTINGandalsoapotentinduceroftypeIIFNs

andothercytokines.

HY-B0180

Imiquimod

TLR7agonist,exhibitsantiviralandantitumoreffects.

6

www.MedChemE

Inhibitors • ScreeningLibraries • Proteins

Compounds

Cat.No.

ProductName

Description

HY-19776

3α-Aminocholestane

SelectiveSHIP1inhibitor.

HY-120635

BMS-1001

OrallyactivehumanPD-L1/PD-1immunecheckpointinhibitor.

HY-13740

Resiquimod

TLR7/TLR8agonistthatinducestheupregulationofcytokines.

HY-16724

Indoximod

Indoleamine2,3-dioxygenase(IDO)pathwayinhibitor.

HY-101111

PF-06840003

highlyselectiveorallybioavailableIDO-1inhibitor.

HY-10219

Rapamycin

PotentandspecificmTORinhibitor,autophagyactivatorand

immunosuppressant.

HY-100453

HO-3867

SelectiveandpotentSTAT3inhibitor,showsantitumoractivity.

HY-100461

C29

TLR2inhibitorblockshTLR2/1andhTLR2/6signaling.

HY-100493

BP-1-102

OrallyavailableinhibitoroftranscriptionfactorStat3.

HY-100678

CGS15943

Orallybioavailablenon-xanthineAdenosineReceptorantagonist.

HY-100747

PSB-12379

Nucleotideanalogue,isapotentCD73inhibitor.

HY-108472

Loxoribine

SelectiveTLR7agonistwithanti-viralandanti-tumoractivities.

HY-110120

DSR-6434

SelectiveTLR7agonisthasastrongantitumorability.

HY-110318

VUF11207fumarate

CXCR7agonist,inducesrecruitmentofβ-arrestin2andsubsequent

internalization.

HY-110353

CU-T12-9

SpecificTLR1/2agonist,invokesanelevationofthedownstream

effectorsTNF-α,IL-10,andiNOS.

HY-128588

STAT3-IN-3

STAT3inhibitorwithanti-proliferativeactivity,inducesapoptosisin

breastcancercells.

HY-13245

PF-4136309

Potent,selective,andorallybioavailableCCR2antagonist.

HY-13406

TAK-779

CCR5/CXCR3antagonist,selectivelyinhibitsR5HIV-1.

CompoundScreeningLibraries

Cat.No.:HY-L031

SmallMoleculeImmuno-OncologyCompoundLibrary

Auniquecollectionof200+bioactivetumor

immunologycompounds.

7

MCE

MasterofBioactiveMolecules

Immunity&Inflammation

Humanimmunesystemiscomposedofinnateimmunityandadaptiveimmunity,inwhichinnateimmunityservedasthefirstlineofdefenseagainstnon-selfpathogens.Uponinfectionortissuedamage,patternrecognitionreceptors(PRRs)ofinnateimmunecellsrecognizepathogen-associatedmolecularpatterns(PAMPs)ordamage-associatedmolecularpatterns(DAMPs),triggeringtheactivationoftranscriptionfactorsNF-κB,AP1orIRF,whicheventuallyledtothetranscriptionofinterferon,proinflammatorycytokinesandchemokines[6].

Overactiveinnateimmunityiscloselyrelatedtoautoimmunediseases,meanwhileinactivatedinnateimmunityrelatedcloselytocancers.Besides,innateimmuneinhibitorsareoftenusedinorgantransplant.

MCEprovideshundredsofimmunity&inflammationrelatedproducts,coveringhottargetsincludingTLR,NLR,RLR,cGAS/STING,etc.

Tumor

cells

Cat.No.

ProductName

HY-12815A

MCC950sodium

HY-18739

PMA

Innateimmunity

Macrophage

Apoptotic

tumorfragments

Dendriticcell

NKcell

Complement

cascade

Plasmacell

Blymphocyte

Cytotoxic

Tcell

Treg T-helper

cell

Adaptiveimmunity

Figure4.Immunesurveillance[7]

Compounds

Description

Potent,selectiveNLRP3inhibitor.

DualSphKandproteinkinaseCactivator,inducesdifferentiationinTHP-1cells.

HY-127105

Iptacopan(LNP023)

HighlyselectivefactorBinhibitor,targetstheunderlyingcauseof

complement3glomerulopathy.

HY-16561

Resveratrol

Anti-oxidant,anti-inflammatory,cardioprotective,andanti-cancer

drugs,hasawidespectrumoftargetsincludingmTOR,JAK,

β-amyloid,Adenylylcyclase,IKKβ,DNApolymerase.

HY-15775

Arginaseinhibitor1

PotentinhibitorofhumanarginasesIandII.

8

www.MedChemE

Inhibitors • ScreeningLibraries • Proteins

Compounds

Cat.No.

ProductName

Description

HY-100381

Nigericinsodiumsalt

AntibioticfromStreptomyceshygroscopicusthatworksbyacting

asanH+,K+,andPb2+ionophore,aNLRP3activator.

HY-103666

CY-09

NLRP3inhibitor,directlybindstotheATP-bindingmotifofNLRP3

NACHTdomain.

HY-111149A

PS372424

Threeamino-acidfragmentofCXCL10,atcasaCXCR3agonist

withanti-inflammatoryactivity.

HY-103362

CCR2antagonist4

PotentandspecificCCR2antagonist,potentlyinhibits

MCP-1-inducedchemotaxis.

HY-107575

TLR4-IN-C34

OrallyactiveTLR4inhibitorandreducessystemicinflammationin

modelsofendotoxemiaandnecrotizingenterocolitis.

HY-11109

Resatorvid

TLR4inhibitor,inhibitsNO,TNF-αandIL-6production.

HY-N0283

Diacerein

Interleukin-1betainhibitor,isaslow-actingmedicineoftheclass

anthraquinoneusedtotreatjointdiseases.

HY-114775

RCGD423

Gp130modulator,whichpreventsarticularcartilagedegeneration

andpromotesrepair.

HY-N0722

Neochlorogenicacid

Orallyactivesteroidalanti-inflammatorydrug(SAID),inhibits

proinflammatorycytokineactivity.

HY-15614

SC144

First-in-class,orallyactivegp130inhibitor.

HY-102084

LMT-28

OrallyactiveandthefirstsyntheticIL-6inhibitorthatfunctions

throughdirectbindingtogp130.

CompoundScreeningLibraries

Cat.No.:HY-L007

Immunology/InflammationCompoundLibrary

Auniquecollectionof3,000+compoundswithbiologicalactivityusedforImmunology/Inflammationresearch.

Cat.No.:HY-L008

JAK/STATCompoundLibrary

Auniquecollectionof250+bioactivecompoundsrelatedtoJAK/STATsignaling.

Cat.No.:HY-L014

NF-κBSignalingCompoundLibrary

Auniquecollectionof500+NF-κBsignalingrelatedsmall

moleculecompounds.

9

MCE

MasterofBioactiveMolecules

Anti-infection

Anti-infectivesaredrugsthatcaneitherkillaninfectiousagentorinhibititfromspreading,whichincludingantibiotics,antibacterials,antifungals,antiprotozoals,etc.

Antibioticsspecificallytreatinfectionscausedbybacteria,mostcommonlyusedtypesofantibioticsare:Aminoglycosides,Penicillins,Fluoroquinolones,Cephalosporins,Macrolides,andTetracyclines.Newotherapproachessuchasphotodynamictherapy(PDT)andantibacterialpeptideshavebeenconsideredasalternativestokillbacteria.

Thehighratesofmorbidityandmortalitycausedbyfungalinfectionsareassociatedwiththecurrentlimitedantifungalarsenalandthehightoxicityofthecompounds.ThemostcommonantifungaltargetsincludefungalRNAsynthesisandcellwallandmembranecomponents,thoughnewantifungaltargetsarebeinginvestigated.Antiprotozoaldrugsaremedicinesthattreatinfectionscausedbyprotozoa.Ofwhich,malariaremainsamajorworldhealthproblemfollowingtheemergenceandspreadofPlasmodiumfalciparumthatisresistanttothemajorityofantimalarialdrugs.

Asoneofthebiggestpublichealthchallengesofourtime,antimicrobialresistancebecomeanincreasingconcernthatneedtobesettledurgently.

MCEhereprovide1,000+potentialanti-infectionreagents,inhopingtohelpyoufindantimicrobialsofthenewgeneration.

Funji

Protozoa

Mastcell

Bacteria

CTL

Plasmacell

B

CD8

Macrophage

IFN-γ

EosinophilBasophil

Tfh

Th1

Th2

Helminth

Virus

Bacteria

(extracellular)

NK

DC

T

Teff

Tregs

Th17

NKT

IL-10/TGF-β

IL-17

Neutrophil

Th2

Th1

Epithelium

Positivesignal/induction/secretion

Negativeregulation/inhibition

Figure5.Schematicrepresentationofthehostimmuneresponseagainstmicrobialpathogens[8]

10

www.MedChemE

Inhibitors • ScreeningLibraries • Proteins

Compounds

Cat.No.

ProductName

Description

HY-17006

Caspofungin

CaspofunginAcetate(MK-0991Acetate)isanantifungaldrug,and

noncompetitivelyinhibits1,3-β-Dglucansynthaseactivity.

HY-10844

Pretomanid

Antibioticusedfortheresearchofmulti-drug-resistanttuberculosis

affectingthelungs.

HY-B0879A

Suraminsodiumsalt

CompetitivePTPasesinhibitor,usedasantiparasitic,anti-neoplastic

andanti-angiogenicagent.

HY-10846

Delamanid

Mycobacterialcellwallsynthesisinhibitor,inhibitsthesynthesisiof

mucolicacids.

HY-10373

Trimetrexate(CI-898)

Potentcompetitiveinhibitorofbacterial,protozoan,andmammalian

dihydrofolatereductase.

HY-17586

Dalbavancin

Semisyntheticlipoglycopeptideantibioticwithpotentbactericidal

activityagainstGram-positivebacteria.

HY-10392

Sutezolid

Orallyactiveoxazolidinoneantimicrobialagent,actsbyinhibiting

bacterialproteinsynthesis.

HY-B1743A

Puromycindihydrochloride

Aminonucleosideantibiotic,inhibitsproteinsynthesis.

HY-128423

Tylvalosintartrate

MacrolideantibioticthatcanagainstGram-positivebacteria.

HY-Y0055

Phenothiazine

Antibiotic,hasinsecticidal,fungicidal,andantibacterialactivities.

HY-N0565B

Doxycyclinehyclate

Antibiotic,isanorallyactiveandbroad-spectrumMMPinhibitor.

HY-16592

BrefeldinA

Lactoneantibioticandaspecificinhibitorofproteintrafficking.

HY-108009A

Rezafunginacetate

Next-generation,broad-spectrum,andlong-lastingechinocandin,

showspotentantifungalactivity.

HY-B0856

ValidamycinA

Fungicidal,isanagriculturalantibiotic.

HY-N1347

Robinetin

Naturallyoccurringflavonoidwithantifungal,antiviral,antibacterial,

antimutagenesis,andantioxidantactivity.

HY-B0490

HygromycinB

HygromycinBisanaminoglycosideantibioticactiveagainst

prokaryoticandeukaryoticcells.

HY-15310

Ivermectin

Broad-spectrumanti-parasiteagent,aspecificinhibitorofImpα/β

1-mediatednuclearimport.

HY-B0318

Metronidazo

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