(
(51)InternationalPatentClassification:
Notclassified
(21)InternationalApplicationNumber:
PCT/US2019/029192(22)InternationalFilingDate:
25April2019(25.04.2019)
(25)FilingLanguage:(26)PublicationLanguage:(30)PriorityData:
62/662,637
25April2018(25.04.2018)
EnglishEnglish
US
(81)DesignatedStates(unlessotherwiseindicated,forevery
kindofnationalprotectionavailable).AE,AG,AL,AM,AO,AT,AU,AZ,BA,BB,BG,BH,BN,BR,BW,BY,BZ,CA,CH,CL,CN,CO,CR,CU,CZ,DE,DJ,DK,DM,DO,DZ,EC,EE,EG,ES,FI,GB,GD,GE,GH,GM,GT,HN,HR,HU,ID,IL,IN,IR,IS,JO,JP,KE,KG,KH,KN,KP,KR,KW,KZ,LA,LC,LK,LR,LS,LU,LY,MA,MD,ME,MG,MK,MN,MW,MX,MY,MZ,NA,NG,NI,NO,NZ,OM,PA,PE,PG,PH,PL,PT,QA,RO,RS,RU,RW,SA,SC,SD,SE,SG,SK,SL,SM,ST,SV,SY,TH,TJ,TM,TN,TR,TT,TZ,UA,UG,US,UZ,VC,VN,ZA,ZM,ZW.(84)DesignatedStates(unlessotherwiseindicated,forevery
kindofregionalprotectionavailable).ARIPO(BW,GH,GM,KE,LR,LS,MW,MZ,NA,RW,SD,SL,ST,SZ,TZ,UG,ZM,ZW),Eurasian(AM,AZ,BY,KG,KZ,RU,TJ,TM),European(AL,AT,BE,BG,CH,CY,CZ,DE,DK,EE,ES,FI,FR,GB,GR,HR,HU,IE,IS,IT,LT,LU,LV,MC,MK,MT,NL,NO,PL,PT,RO,RS,SE,SI,SK,SM,TR),OAPI(BF,BJ,CF,CG,Cl,CM,GA,GN,GQ,GW,KM,ML,MR,NE,SN,TD,TG).
(71)Applicant:CHARLESR.DREWUNIVERSITYOF
MEDICINEANDSCIENCE[US/US];1731East120thStreet,LosAngeles,California90059(US).(72)Inventors:WU,Yong;1731East120thStreet,LosAn?
geles,California90059(US).VADGAMA,Jay;1731East120thStreet,LosAngeles,California90059(US).HUANG,Zhimin;1731East120thStreet,LosAngeles,California90059(US).WU,Ke;1731East120thStreet,LosAngeles,California90059(US).(74)Agent:FORCE,WalkerR.;c/oPillsburyWinthropShaw
PittmanLLP,P.O.BOX10500,McLean,Virginia22101(US).
Published:
—withoutinternationalsearchreportandtoberepublished
uponreceiptofthatreport(Rule48.2(g))
(54)Title:NOVELMCT4INHIBITORSANDUSESTHEREOF
Fig.9A
Days
(57)Abstract:PresentedhereinareMCT4inhibitorsandusesthereoffortreatingcancer.
NOVELMCT4INHIBITORSANDUSESTHEREOF
RELATEDPATENTAPPLICATIONS
[0001]
ThispatentapplicationclaimsthebenefitofU.S.ProvisionalPatentApplication
No.62/662,637filedonApril25,2018,entitledNOVELMCT4INHIBITORSANDUSES
THEREOF,namingYongWu,JayVadgama,ZhiminHuangandKeWuasinventors,anddesignatedbyAttorneyDocketNo.033246-0458760.FIELDOFTHEINVENTION
[0002]Embodimentsrelatetonovelinhibitorsofmonocarboxylatetransporter4(MCT4),
andusesthereoffortreatingcancer.INTRODUCTION
[0003]Monocarboxylatetransporter4(MCT4,alsoknownasSLC16A3)isacell-surface
expressedmonocarboxylatetransporter.MCT4isthoughttocatalyzetherapidtransportofmanymonocarboxylatessuchaslactate,pyruvate,branched-chainoxoacidsderivedfromleucine,valineandisoleucine,andtheketonebodiesacetoacetate,beta-hydroxybutyrateandacetate,acrosstheplasmamembrane.MCT4expressionishighlyup-regulatedinmany
cancers,anditsexpressioncorrelateswithpoorsurvival,inmanycancerindications.
[0004]UpregulationofaerobicglycolysisandahighdemandforATPiscommoninmany
cancertypes,aphenomenonknownastheWarburgeffect.Cancercellstypicallyimportmassiveamountsofglucosewhicharefunneledthroughanoveractiveglycolysismetabolicpathway.TheexcessivelyproducedpyruvateisthenconvertedtolargeamountsoflactatebytheactivityoftheLDHenzyme.Itisspeculatedthatcancercellsupregulatetheexpressionofcell-surfaceMCT4tomanagewiththesecretionofexcessivelyproducedlactateandtopreventintracellularacidosis.MCT4silencinghasbeenshowntorepressand/orablatestumorgrowthinxenograftmodelsofbreastcancer,colorectalcancer,andglioma.
[0005]PresentedhereinarenovelMCT4inhibitorsandusesthereoftotreatcancer.[0006]Certainaspectsofthetechnologyaredescribedfurtherinthefollowingdescription,
examples,claimsanddrawings.
BRIEFDESCRIPTIONOFTHEDRAWINGS
WO2020033019A2NOVELMCT4INHIBITORSANDUSESTHEREOF - 图文
