Sheng tshuaj nyob rau lub Kaum Ib Hlis 10 (hnub no) hauv nws WeChat tshaj tawm rau pej xeem hais tias (tus thawj hauv qab no), lub tuam txhab hauv kev tshawb fawb thawj chav kawm tshiab 1 embryonic ectodermal development protein (EED) inhibitor APG-5918 tau txais kev tswj hwm tshuaj hauv tebchaws (NMPA) Lub chaw tshuaj xyuas tshuaj (CDE) daim ntawv tso cai soj ntsuam kuaj mob, yuav ua tiav cov kev kho mob ntawm cov qog nqaij hlav siab lossis hematological malignancy theem I kev sim tshuaj.
Ua ntej qhov no, kev tshawb fawb ntau yam tau pom zoo hauv Tebchaws Meskas los ua cov kev sim tshuaj rau cov qog nqaij hlav siab lossis cov qog ntshav qhia, uas yog lwm qhov kev ua tiav ntawm lub tuam txhab "Tuam Tshoj-Us Ob Chav Xov Xwm" lub tswv yim, pib paub txog kev txhawb nqa synchronous. ntawm Tuam Tshoj thiab Tebchaws Meskas. APG-5918 yog thawj thawj Suav tshawb fawb EED inhibitor nkag mus rau theem kho mob.
Qhov no yog multicenter, qhib-label theem I dose-escalation thiab dose-expansion soj ntsuam kuaj sim tsim los soj ntsuam kev nyab xeeb, pharmacokinetics, thiab kev ua tau zoo ntawm qhov ncauj APG-5918 nyob rau hauv cov neeg mob uas muaj siab tawv nqaij hlav los yog hematologic malignancies. Xu Ruihua, tus thawj tswj hwm ntawm Tuam Tshoj Society of Clinical Oncology thiab tus thawj coj ntawm Lub Chaw Tiv Thaiv Kab Mob thiab Kev Kho Mob ntawm Sun Yat-sen University, yuav ua tus thawj coj tshawb nrhiav (PI) ntawm kev sim tshuaj.
EZH2 tau qhia ntau yam hauv tib neeg cov qog noj ntshav thiab txhawb nqa kev loj hlob ntawm cov qog nqaij hlav cancer thiab malignant degeneration, thiab tsom inhibition ntawm methyltransferase kev ua ntawm EZH2 tau pom tias yog kev kho mob qog noj ntshav zoo. Txawm li cas los xij, kev hloov pauv theem nrab hauv EZH2 tuaj yeem lees paub cov tshuaj tiv thaiv tau txais, thiab nws cov homology, EZH1, kuj tseem muaj cov haujlwm methyltransferase, ob qho tib si ua rau muaj kev txwv EZH2 inhibitor. Nws tau pom tias cov polyproteinogenicity ntawm PRC2 complex thiab EZH2 kev ua haujlwm yog nyob ntawm kev ua haujlwm thiab kev tswj hwm ntawm EED. Cov tshuaj uas inhibit PRC2 subunit EED cuam tshuam cov protein - protein sib cuam tshuam (PPI) ntawm EED-EZH2, ua rau PRC2 ua haujlwm tsis zoo, ua rau poob ntawm PRC2 kev ua haujlwm txhawb nqa los ntawm H3K27me3, thiab tiv thaiv trimethylated [1] ntawm H3K27. Yog li ntawd, kev tsom mus rau EED cov proteins tau txais txiaj ntsig zoo raws li lwm txoj hauv kev ua kom tsis muaj zog los tiv thaiv PRC2.
APG-5918 yog ib qho tshiab me me molecule inhibitor ntawm EED protein nquag thiab xaiv heev. Nws muaj siab affinity. Los ntawm kev tswj cov qog nqaij hlav epigenetics thiab qog microenvironment, nws muaj cov ntaub ntawv kho mob dav dav hauv cov qog ntshav, cov qog nqaij hlav thiab cov tsos mob tsis yog qog. APG-5918 tuaj yeem xaiv khi rau H3K27me3 sau npe ntawm EED protein, ua rau muaj kev hloov pauv hauv EED H3K27me3 khi hnab ris, tiv thaiv kev cuam tshuam ntawm EED nrog histone methyltransferase EZH2. Cov ntaub ntawv ua ntej qhia tau hais tias qhov antitumour viability ntawm APG-5918 hauv vitro antitumour cell proliferation viability nyob rau hauv ntau cov qog cell thiab hauv PDX / CDX qauv ntawm EZH2-mutant B cell non-Hodgkin's lymphoma, INI{{13} }negative malignant rhabdomyoma, BAP1-mutated mesothelioma, thiab prostate cancer.
Xu Ruihua, tus thawj coj thiab tus thawj coj ntawm Lub Chaw Tiv Thaiv thiab Tswj Kab Mob ntawm Sun Yat-sen University, tau hais tias:
Targeting PRC2 complex proteins, tshwj xeeb tshaj yog EED, tej zaum yuav siv tau nyob rau hauv cov qog nqaij hlav nrog qee yam caj ces. EED inhibitor APG-5918 tau qhia meej lub hom phiaj-binding cuam tshuam thiab lub hom phiaj muaj feem cuam tshuam txog kev ua haujlwm hauv vitro thiab tsiaj hauv vivo kev soj ntsuam. Cov kev tshawb fawb soj ntsuam ntxiv yog tsim nyog los tshawb txog nws txoj kev ua tau zoo. Targeting PRC2 complex proteins, tshwj xeeb tshaj yog EED, tej zaum yuav siv tau nyob rau hauv cov qog nqaij hlav nrog qee yam caj ces. EED inhibitor APG-5918 tau qhia meej meej lub hom phiaj-binding cuam tshuam thiab lub hom phiaj cuam tshuam txog kev ua haujlwm hauv vitro thiab tsiaj hauv vivo kev soj ntsuam. Cov kev tshawb fawb soj ntsuam ntxiv yog tsim nyog los tshawb txog nws txoj kev ua tau zoo.
Dr. Zhai Yifan, tus thawj kws kho mob ntawm Yasheng Pharmaceutical, tau hais tias:
Qhov no yog lwm qhov kev vam meej loj tom qab kev pom zoo ntawm APG-5918 cov kab mob qog nqaij hlav hauv Tebchaws Meskas, thiab tseem yog qhov kev xav ntawm asasheng txoj kev ua raws li Sino-US lub tswv yim thiab lub zog tshiab thoob ntiaj teb. Peb tos ntsoov yuav ua hauj lwm ua ke nrog Thawj Tswj Hwm Xu kom nquag txhawb kev kho mob ntawm APG-5918 thiab tau txais txiaj ntsig ntau dua rau cov neeg mob sai li sai tau.
