WhatIsPoziotinibAndWhereToBuyTheBestPoziotinibPeptide -ByPhcoker
PoziotinibStructure
Sequence: /
Molecular
Formula: C23H21Cl2FN4O3
Molecular Weight: 49134g/mol
PubChemCID:25127713
CASNumber:1092364-38-9
Synonyms: NOV120101，HM781-36B，UNII-OEI6OOU6IK
1.PoziotinibHistory
Poziotinib(NOV120101,HM781-36B)isadrugindevelopmentbyHanmiPharmaceutical(SouthKorea), LuyePharma(China),andSpectrumPharmaceuticals(restoftheworld)forvariouscancers Builtonananilino-quinazolinescaffold,PoziotinibinhibitstheepidermalgrowthfactorreceptorsEGFR, HER2/neu,andHER4bybindingcovalentlytoitstargetsThismechanismblocksthetyrosinekinase
activityofthesereceptors,impedingdownstreamsignalingpathwaysessentialfortumorcellproliferation andsurvival,ultimatelyleadingtocelldeath
DiscoveredbyHanmiPharmaceutical,Poziotinib'sdevelopmenthasinvolvedstrategiclicensing agreements
InAugust2014,HanmiexclusivelylicensedtherightsforChinatoLuyePharma; InFebruary2015,theylicensedtherightsfortherestoftheworldoutsideSouthKoreatoSpectrum Pharmaceuticals
Asof2016,SpectrumPharmaceuticalsinitiatedaPhaseIIclinicaltrialofPoziotinibasasecond-line treatmentforbreastcancer
DevelopmentTimelineforPoziotinib
Date Article
Nov25,2022
Sep22,2022
Feb11,2022
Dec6,2021
Mar11,2021
Sep24,2018
SpectrumPharmaceuticalsReceivesCompleteResponseLetter fromUSFoodandDrugAdministrationforPoziotinib
SpectrumPharmaceuticalsProvidesUpdateonPoziotinibFollowing FDAOncologicDrugsAdvisoryCommitteeMeeting
SpectrumPharmaceuticalsAnnouncesAcceptanceofNewDrug ApplicationFilingforPoziotinib
SpectrumPharmaceuticalsAnnouncesAcceptanceofNewDrug ApplicationFilingforPoziotinib
FDAGrantsFastTrackDesignationtoSpectrumPharmaceuticals’ Poziotinib
SpectrumPharmaceuticalsAnnouncesReleaseofUpdated PoziotinibDataFromMDAndersonPhase2StudyinNon-SmallCell LungCancerPatients
PoziotinibResearchesonCancers
PoziotinibhasbeeninvestigatedinclinicaltrialsforthetreatmentofvariouscancersSomeofthe specificconditionsstudiedinclude:
BreastCancer
MetastaticBreastCancer
IncreasedDrugResistance
AdenocarcinomaofLungStageIV
AdenocarcinomaofLungStageIIIB
ThesetrialsexploretheeffectivenessofPoziotinibintargetingcancersthatoverexpressorhave mutationsintheepidermalgrowthfactorreceptors(EGFR),includingHER2andHER4Itsuseis particularlyfocusedoncancerswithEGFRexon20insertionmutations
2.WhatisPoziotinib?
Poziotinibpeptideisanorallybioavailable,quinazoline-based,small-molecule,irreversible pan-epidermalgrowthfactorreceptor(EGFRorHER)inhibitorwithpotentialantineoplasticactivity.It inhibitsEGFR(HER1orErbB1),HER2,HER4,andEGFRmutants,therebyhinderingtheproliferationof tumorcellsthatoverexpressthesereceptors.EGFRs,whicharecellsurfacereceptortyrosinekinases, arefrequentlyupregulatedinvariouscancercelltypesandplaycrucialrolesincellularproliferationand survival
Poziotinibhasbeeninvestigatedinclinicaltrialsforthetreatmentofvariouscancers,includingbreast cancer,metastaticbreastcancer,increaseddrugresistance,adenocarcinomaofthelung(StageIVand StageIIIB),amongothers.
Foryoursafety,pleasebuyandusePoziotinibwithcaution
3.WhataretheMechanismofPoziotinib?
ThemechanismofactionofPoziotinibinvolvesitssmallsizeandflexiblestructure,whichallowitto accesstherestrictedbindingsitesofepidermalgrowthfactorreceptors(EGFRs),includingHER1 (ErbB1),HER2,andHER4,aswellasEGFRmutantsByovercomingthesterichindrancethatmight impedeothermolecules,Poziotinibeffectivelybindstothesereceptorsandinhibitstheirtyrosinekinase activity
Inhibitionoftyrosinekinaseactivityblocksthedownstreamsignalingpathwaysthatarecriticalforcell proliferationandsurvivalAsaresult,thisleadstothedisruptionofcellularprocessesessentialfortumor growthandprogression,ultimatelycausingcelldeathThismechanismmakesPoziotinibapotent antineoplasticagent,particularlyeffectiveagainstcancerswithoverexpressedormutatedEGFRs
Ifyouarefacingtheproblemofcancerresearch,youmightaswelltrytobuyPoziotinibforatryBesure tobuyPoziotinibfromaregularsource,buyPoziotinibonlineisnotabadchoice,theimportantistofind areliablePoziotinibmanufacturer
4.WhatBenefitsCanYouGetFromPoziotinibonNSCLC?
TheantitumoractivityofpoziotinibwasfoundtobesignificantinpatientswithEGFRexon20positive non–smallcelllungcancer(NSCLC).Theefficacyofthetreatmentwasfoundtobehighlydependenton thelocationoftheexon20loopinsertionThesefindingswerepublishedinCancerCellTheresults werepublishedinCancerCell
Thestudy,designatedasphase2(NCT03066206),included50patientswithadvancednon-smallcell lungcancer(NSCLC)whoexhibitedpointmutationsorinsertionsintheEGFRexon20Thestudy achieveditsprimaryendpointwithaconfirmedobjectiveresponserate(ORR)of32%(95%CI, 20.7%-45.8%)and31%(95%CI,19.1%-46%)byinvestigatorandblindedindependentreview, respectively
Moreover,researchersfoundamedianprogression-freesurvival(PFS)of5.5months(95%CI,5.4-10.4) withaPFSrateof43%(95%CI,30%-60%)at6months,and29%(95%CI,18%-46%)at12months
Medianoverallsurvivalalsoappearedtobebeneficialat192months(95%CI,118-241)withadisease controlrateof84%(95%CI,715%-92%)
“EGFRexon20mutantlungcancerstypicallydon’trespondwelltothetypesoftyrosinekinaseinhibitors thathavebeenlargelysuccessfulintargetingclassicalEGFRmutations,leavingthispatientpopulation withfeweffectivetreatmentoptions,”saidseniorauthorofthestudy,JohnHeymach,MD,PhD,chairof theThoracic/Head&NeckMedicalOncologyattheMDAndersonCancerCenter,inapressrelease.2
“Ourstudygiveshopefornotonlyapotentiallybeneficialtreatmentoption,butforanewlevelof precisiontobettertargetEGFRexon20mutationsandtodesignmoreeffectiveclinicaltrials”
AnewdrugapplicationforpoziotinibwasacceptedbytheFDAforpatientswithadvancedormetastatic NSCLCharboringHER2exon20insertionmutationsinFebruary2022Poziotinibalsoreceivedfast trackdesignationfromtheFDAinMarch2021forpatientswithHER2exon20insertion–mutated NSCLC.
5.SideeffectsofSemaglutide
Poziotinib,likemanytargetedcancertherapies,isassociatedwitharangeoftreatment-relatedadverse events(TRAEs)AlmostallpatientsenrolledinclinicaltrialsexperiencedTRAEsofanygradeThemost commonsideeffectsinclude:
Diarrhea:Experiencedby79%ofpatients
Rash:Experiencedby60%ofpatients
Stomatitis(inflammationofthemouth):Experiencedby52%ofpatients
Paronychia(nailinfection):Experiencedby45%ofpatients
Severe(Grade3)TRAEswerealsoreportedinasignificantproportionofpatients,occurringin60%of casesThemostcommonseveresideeffectsinclude:
Diarrhea:Experiencedby25%ofpatients
Rash:Experiencedby28%ofpatients
Thesesideeffectshighlighttheneedforcarefulmanagementandmonitoringofpatientsundergoing treatmentwithPoziotinib
ReferencedCitations
[1]LeX,CornelissenR,GarassinoM,etalPoziotinibinNon-Small-CellLungCancerHarboringHER2 Exon20InsertionMutationsAfterPriorTherapies:ZENITH20-2TrialJClinOncol2022;40(7):710-771
[2]Phase2StudyofPoziotinibinPatientsWithNSCLCHavingEGFRorHER2Exon20Insertion Mutation.AccessedonJune5,2022.
[3]ElaminYY,RobichauxJP,CarterBW,etalPoziotinibforPatientsWithHER2Exon20Mutant Non-Small-CellLungCancer:ResultsFromaPhaseIITrialJClinOncol2022;40(7):702-709
[4]SpectrumPharmaceuticalsreceivescompleteresponseletterfromusfoodanddrugadministration forpoziotinib;ReaffirmsfocusonthecommercializationofROLVEDON™(eflapegrastim-xnst)injection NewsreleaseSpectrumPharmaceuticalsNovember25,2022AccessedNovember28,2022
[5]LeX,CornelissenR,GarassinoM,etal.Poziotinibinnon-small-celllungcancerHarboringHER2 exon20insertionmutationsafterpriortherapies:ZENITH20-2Trial.JClinOncol.2022;40(7):710-718. doi:10.1200/JCO.21.01323
[6]KimM(4July2016)"HanmiPharmaceuticaltoStepUpR&DInvestmenttoFurtherDevelopCore Technologies"BusinessKorea
[7]RoskoskiR(September2014)"ErbB/HERprotein-tyrosinekinases:Structuresandsmallmolecule inhibitors"PharmacologicalResearch87:42–59doi:101016/jphrs201406001PMID24928736
[8]Poziotinib"NCIDrugDictionaryNationalCancerInstitute,NationalInstitutesofHealth,US DepartmentofHealthandHumanServicesRetrieved25March2017
[9]J.RobertMcCorkle,JustinW.Gorski,JinpengLiu,etal.Lapatinibandpoziotinibovercome ABCB1-mediatedpaclitaxelresistanceinovariancancer,PLOSONE(2021) DOI:101371/journalpone0254205
[10]OncologicDrugsAdvisoryCommittee(ODAC)MeetingFDASeptember22,2022Accessed November28,2022
[11]SpectrumPharmaceuticalsannouncesacceptanceofnewdrugapplicationfilingforpoziotinib NewsreleaseSpectrumPharmaceuticalsFebruary11,2022AccessedNovember28,2022
[12]SchulerM,AwadaA,HarterP,CanonJL,PossingerK,SchmidtM,etal.(August2012)."AphaseII trialtoassessefficacyandsafetyofafatinibinextensivelypretreatedpatientswithHER2-negative metastaticbreastcancer"BreastCancerResearchandTreatment134(3):1149–59 doi:101007/s10549-012-2126-1PMC3409367PMID22763464
[13]LinNU,WinerEP,WheatleyD,CareyLA,HoustonS,MendelsonD,etal(June2012)"AphaseII studyofafatinib(BIBW2992),anirreversibleErbBfamilyblocker,inpatientswithHER2-positive metastaticbreastcancerprogressingaftertrastuzumab"BreastCancerResearchandTreatment133 (3):1057–65
[14]LiD,AmbrogioL,ShimamuraT,KuboS,TakahashiM,ChirieacLR,etal(August2008) "BIBW2992,anirreversibleEGFR/HER2inhibitorhighlyeffectiveinpreclinicallungcancermodels"
Oncogene27(34):4702–11doi:101038/onc2008109PMC2748240PMID18408761
[15]MillerVA,HirshV,CadranelJ,ChenYM,ParkK,KimSW,etal(May2012)"Afatinibversus placeboforpatientswithadvanced,metastaticnon-small-celllungcancerafterfailureoferlotinib, gefitinib,orboth,andoneortwolinesofchemotherapy(LUX-Lung1):aphase2b/3randomisedtrial".
TheLancet.Oncology.13(5):528–38.doi:10.1016/S1470-2045(12)70087-6.PMID22452896.
Authorofthisarticle:
DrJeanZenggraduatedfromking’scollegelondonFacultyofLifeSciences&Medicine
ScientificJournalpaperAuthor:
1RobinCornelissenMD,PhD
PulmonaryMedicine,ErasmusMCCancerInstitute,Rotterdam,TheNetherlands
2.YasirY.Elamin
DepartmentofThoracic/HeadandNeckMedicalOncology,TheUniversityofTexasMDAnderson CancerCenter,Unit432,POBox301402,1500HolcombeBoulevard,Houston,TX77030,USA
3XLe
MDAndersonCancerCenter,Houston/TX/USA
4FrankJBormMD
DepartmentofPulmonaryDiseases,LeidenUniversityMedicalCentre,Leiden,TheNetherlands
5.ReidOldenburgMD,PhD
DepartmentofDermatology,UniversityofCaliforniaSanDiego,LaJolla,SanDiego,California