Eprenetapopt + azacitidine Siv Tau Zoo! --- 1/2 ib

AML yog hom mob ntshav qab zib ntau tshaj rau cov neeg laus thiab muaj qhov tshwm sim ntau tshaj plaws hauv tib neeg 60 xyoo thiab laus dua. Tus kab mob no yog tus yam ntxwv txawv txav, tsis paub tab ntawm cov qe ntshav dawb loj hlob, uas cuam tshuam rau kev tsim cov qe ntshav ib txwm muaj. AML tej zaum yuav yog qhov tshiab, theem thib ob ntawm kev txhim kho ntawm lwm yam kab mob hematological, lossis vim muaj qhov ua tsis zoo yav dhau los kho los ntawm kev siv tshuaj kho mob lossis kho hluav taws xob. Kev kwv yees ntawm AML theem ob yog qhov phem dua li ntawm AML tshiab. TP53 kev hloov pauv tau cuam tshuam nrog kev kwv yees tsis zoo. Kwv yees li 20% ntawm cov neeg mob AML tshiab, ntau dua 30% ntawm kev kho mob ntsig txog AML cov neeg mob, thiab 70-80% ntawm cov neeg mob karyotypes nyuaj muaj TP53 hloov pauv.

Cov noob p53 qog tiv thaiv kab mob yog cov noob ntau tshaj plaws hauv tib neeg cov qog, suav txog 50% ntawm tib neeg cov qog. Cov kev hloov pauv no feem ntau cuam tshuam nrog kev siv tshuaj tiv thaiv kab mob qog noj ntshav thiab tsis muaj txoj sia nyob tas mus li, thiab sawv cev rau qhov tsis xav tau kev kho mob loj hauv kev kho mob qog noj ntshav.

eprenetapopt mechanism ntawm kev nqis tes ua

eprenetapopt (APR-246) yog cov qauv me me uas tuaj yeem rov ua haujlwm ntawm kev hloov pauv p53 thiab ua rau apoptosis. eprenetapopt yog prodrug uas tuaj yeem hloov pauv mus rau hauv cov khoom sib xyaw ua ke methylene quinuclidinone (MQ), uas yog Michael tus neeg txais khoom uas khi rau kev hloov pauv p53 los ntawm cysteine ​​thiab rov kho cov tsiaj qus yam hloov pauv thiab ua haujlwm ntawm p53. eprenetapopt tau pom tias rov ua haujlwm hloov pauv thiab tsis ua haujlwm p53 cov protein, yog li ua kom muaj phiaj xwm tuag ntawm tib neeg cov qog nqaij hlav cancer.

eprenetapopt tau pom ua ntej kev tiv thaiv qog ua haujlwm hauv ntau yam mob qog noj ntshav thiab mob qog noj ntshav, suav nrog MDS, AML, thiab mob qog noj ntshav ntawm zes qe menyuam. Ib qho ntxiv, eprenetapopt tau pom tias muaj kev sib koom ua ke zoo nrog cov tshuaj anticancer ib txwm muaj (xws li kev siv tshuaj kho mob) nrog rau cov txheej txheem tshiab raws li tshuaj tua kab mob qog noj ntshav thiab tshuaj tiv thaiv kab mob tiv thaiv kab mob.

Ntxiv rau kev sim tshuaj ua ntej, theem 1/2 qhov phiaj xwm kho mob tau ua tiav, uas tau lees paub tias eprenetapopt muaj kev nyab xeeb zoo, lom neeg thiab paub tseeb cov lus teb kho mob hauv hematological malignancies thiab cov qog nqaij hlav nrog TP53 noob hloov pauv. Qhov tseem ceeb theem 3 kev sim tshuaj kho mob ntawm eprenetapopt ua ke nrog azacitidine (AZA) rau thawj txoj kab kev kho mob ntawm TP53 hloov chaw MDS tau ua tiav, tab sis thawj qhov txheeb cais qhov kawg ntawm kev tshem tawm tag nrho (ORR) tsis tau mus txog. Theem 1/2 qhov kev sim tshuaj ntawm eprenetapopt ua ke nrog venetoclax thiab azacitidine (AZA) hauv thawj txoj kab kev kho mob ntawm TP53 hloov pauv AML mus txog qhov ua tau zoo kawg ntawm qhov ua tiav cov lus teb (CRR). Tam sim no, lwm qhov kev sim tshuaj ntawm eprenetapopt rau kev kho mob ntawm hematological malignancies thiab cov qog nqaij hlav tseem tab tom ua.

Hauv Tebchaws Meskas, FDA tau tso cai eprenetapopt kev tsim cov tshuaj tsim (BTD), kev tsim tshuaj menyuam ntsuag (ODD), thiab kev teev npe nrawm (FTD) rau kev kho MDS. Ib qho ntxiv, FDA tseem tso cai eprenetapopt ODD thiab FTD rau kev kho AML. Hauv Tebchaws Europe, European Medicines Agency (EMA) tseem tau tso cai eprenetapopt lub npe menyuam yaus tshuaj rau kev kho MDS thiab AML.

Ntxiv rau eprenetapopt, Aprea kuj tseem muaj tshuaj APR-548, uas yog lub cim tshiab ntawm cov tshuaj p53 me me molecule, uas qhia tau hais tias muaj qhov ncauj txaus hauv lub cev hauv TP53 cov kab mob qog noj ntshav hloov pauv, thiab tau ua kom muaj txiaj ntsig zoo dua piv nrog eprenetapopt. Nws muaj txiaj ntsig zoo thiab pom tias muaj kev cuam tshuam ntawm kev loj hlob ntawm cov qog hauv vivo tom qab kev tswj hwm qhov ncauj rau cov qog qog noj ntshav.