Xwm Sub-Journal: PI3K inhibitors tab tom yuav pib ua rau muaj kev sib kis loj

Phosphatidylinositol 3-kinase (PI3K) tau nthuav dav dav hauv kev mob qog noj ntshav thiab tiv thaiv kab mob, ua rau tib neeg mob siab rau lawv tus kheej rau kev txhim kho kev kho PI3K inhibitors. Txawm hais tias muaj teeb meem xws li tsis kam siv tshuaj tiv thaiv kab mob thiab tiv thaiv tshuaj, qee qhov PI3K inhibitors tau pom zoo rau kev lag luam, thiab ntau kaum hom kev xaiv thiab tus kheej yias-PI3K inhibitors yog nyob rau theem kev kho mob. Nws cia siab tias yuav muaj ntau ntxiv nyob rau yav tom ntej. Ntau yam PI3K inhibitors tau pib. Peb kwv yees tias thaj chaw ntawm PI3K inhibitors tab tom yuav pib ua rau muaj kev tawg loj, thiab nws cia siab tias cov tshuaj thaiv kab mob yuav pib ua lag luam.

Xwm Xwm sub-Journal luam tawm kev tshuaj xyuas PI3K inhibitor kev tshawb fawb, sib sau cov txiaj ntsig tseem ceeb hauv kev tshawb fawb soj ntsuam txhawm rau txhawb nqa kev thov ntxiv ntawm PI3Kα thiab PI3Kδ inhibitors, thiab sau cov ntsiab lus qhia thiab cov hauv kev rau yav tom ntej hauv daim teb no. Ntxiv rau kev tsom mus rau cov qog noj ntshav qog noj ntshav, cov pov thawj tshiab qhia txog lub peev xwm ntawm PI3K inhibitors hauv kev kho mob qog noj ntshav. Kab lus no tshuaj xyuas qhov kev tshawb pom tseem ceeb hauv kev tshawb fawb soj ntsuam txhawm rau txhawb nqa kev thov ntxiv ntawm PI3Kα thiab PI3Kδ inhibitors, thiab sau cov ntsiab lus qhia thiab cov hauv kev rau yav tom ntej hauv daim teb no.

Phosphatidylinositide 3-kinases (PI3K) yog intracellular phosphatidylinositol kinase uas muaj phosphatidylinositol kinase kev ua haujlwm nrog rau kev ua haujlwm serine/threonine (Ser/Thr) kinase.

PI3K tuaj yeem faib ua peb pawg, ntawm qhov kev kawm dav tshaj plaws yog kuv ntaus PI3K. Hom PI3K no yog heterodimer suav nrog cov cai tswj hwm p85 thiab catalytic subunit p110 (nkag los ntawm PIK3CA gene). Muaj plaub hom catalytic subunits: α, β, δ, γ, γ. Ntawm lawv, α, β, thiab δ sib raug rau p85α, p85β lossis p55 cov cai tswj hwm; thiab γ sib raug rau p101 thiab p84/87 cov cai tswj hwm. Cov cai tswj hwm subunit muaj SH2 sau npe, uas tuaj yeem paub txog intracellular kinase domain ntawm RTKs thiab ua rau muaj kev ua haujlwm ntawm catalytic subunit p110.

Hauv vitro thiab xenograft qog qauv kev tshawb fawb, nws tau pom tias PI3K inhibitors muaj cov tshuaj tiv thaiv kev loj hlob ntawm cov qog nqaij hlav cancer, ntau dua li cytotoxicity; Txawm li cas los xij, nws tsis tuaj yeem txiav txim siab tias PI3K inhibitors tuaj yeem cuam tshuam rau cov qog nqaij hlav thiab qog nqaij hlav, mob angiogenesis, thiab lub cev tiv thaiv kab mob. Cov nyhuv ua ke ua rau tuag ntawm cov qog nqaij hlav cancer.

Cov pov thawj tshiab qhia pom tias PI3K inhibitors tsis xav tau kev tswj xyuas tas li. Kev tswj tsis tu ncua tsis yog tsuas yog ua tau zoo dua, tab sis kuj tseem yuav ua tau zoo dua li kev tiv thaiv kab mob qog noj ntshav.

Kev ua siab ntev ntawm PI3K inhibitors tseem yog teeb meem. Cov xwm txheej tsis zoo suav nrog hyperglycemia, raws plab, tiv thaiv kab mob muaj kuab lom thiab kis kab mob. Txhim kho qhov kev xaiv ntawm PI3K isomers yuav yog tus yuam sij rau kev txhim kho ntxiv ntawm cov tshuaj tiv thaiv.

Txog PI3Kα inhibitors, txoj kev txhim kho tseem ceeb yuav yog kev txiav txim siab ntawm kev tso tshuaj ntau ntxiv raws li kev kho ua ke kom ua rau muaj kev nkag siab zoo ntawm mob qog noj ntshav mis.

Kev ua haujlwm lom ntawm PI3Kδ yog qhov nyuaj dua li qhov xav tau. Txwv tsis pub PI3Kδ hauv vivo thaum soj ntsuam qhov tshwm sim ntawm kev tiv thaiv kev tiv thaiv kab mob thiab kev tiv thaiv kab mob, uas ua rau muaj kev cov nyom rau kev tiv thaiv PI3Kδ mus sij hawm ntev los kho qhov mob thiab cov kab mob autoimmune. Tam sim no, nws tseem tsis tau meej meej tias cov kev phom sij no tshwm sim los ntawm kev sib xyaw ua rau lwm yam PI3K subtypes xws li PI3Kγ.

Tam sim no, PI3Kδ inhibitors feem ntau yog siv hauv kev kho mob qog noj ntshav ntau yam suav nrog B-cell malignancies thiab cov qog nqaij hlav. Kev ua haujlwm ntawm PI3Kδ hauv B-cell malignancies tau lees paub, tab sis vim nws muaj tshuaj lom, PI3Kδ inhibitors tau muab tso ua qhov kev xaiv kho mob rau lwm yam tshuaj tshiab thiab/lossis kev kho mob tsis ua haujlwm.

Qhov kev tshawb fawb tau tshwm sim hauv cov neeg mob CLL yog qhov kev cuam tshuam kev kho mob tshwm sim los ntawm cov xwm txheej tsis zoo tsis muaj kev cuam tshuam tsis zoo rau kev kho mob, thiab qhov tseeb txhim kho kev muaj sia nyob tag nrho. Peb kwv yees tias tsawg kawg qee qhov xwm txheej tsis zoo yog cov cim ntawm kev txhawb nqa cov tswv yim tiv thaiv kab mob, uas tuaj yeem siv los tiv thaiv qog nqaij hlav tiv thaiv kab mob.