Carboxylesterases (CES) Hauv cov tshuaj metabolism: Cov tshuaj tiv thaiv Phenotyping thiab DDI

Cov Ntsiab Lus: Tshuaj siv tshuaj (DDI), carboxylestse carboxylests, ces1, kab mob motalesteresase, tshuaj lom neeg stability, cov tshuaj tsw phenotyping.

Iphas khoom

Lub hauv paus rau phau ntawv

Carboxylesterases (CES) yog qhov tseem ceeb hydrolytic enzymes koom nrog hauv cov metabolism ntawm ntau cov Ester - Thiab kuv nyob rau hauv app. Ntawm cov no,Carboxylesteresase 1 (CES1)thiabCarboxylesteresase 2 (CEST2)yog qhov tseem ceeb tshaj plaws hauv tib neeg. Lawv cov ntaub so ntswg sib luag thiab substrate tshwj xeeb ua rau Ces1 thiab Ces2 Central to nkag siab txog cov tshuaj metabolism,Metabolic Stability, thiabKev Siv Tshuaj - Cov Kev Sib Tham Yeeb Tshuajhauv kws tshawb fawb sciences.

CES1 THIAB CES2: Cov Qauv Txheej Txheem thiab Kev Ua Haujlwm Zoo

Carboxylesteresase 1 (CES1) yog qhia heev hauv daim siab thiab yog ib txwm hu ua tusMob siab carboxylalestsCov. Cov enzyme no tau paub txog nws cov kev dav dav substrate tshwj xeeb, cov tshuaj me xws li oseltamivir, methylfhard, thiab clopidogiRel. Hauv kev sib piv, Carboxylesteresase 2 (CES2) yog ntau tshaj nyob rau hauv txoj hnyuv, li no nws feem ntau hu ua lubMob plab caroxylesteraseCov. CES2 ua lub luag haujlwm tseem ceeb hauv cov metabolism ntawm anticancer cov neeg sawv cev zoo li irinotecan thiab prodrugs xws li capecitabine.

Cov ntsiab lus sib txawv ntawm CES1 thiab Ces2 ua rau lawv cov hom phiaj tseem ceeb hauv kev pom zoo (kev nqus, kev faib tawm, thiab ua kom zoo) profiling. Ob leeg them lub siab carboxylesterase (Ces1) thiab cov hnyuv carboxylester (CES2) tau raug ntsuas thaum ntxov ntawm kev txhim kho kev tsim tshuaj.

Lub luag haujlwm hauv Tshuaj Yeeb Tshuaj Nyob Hauv Tshuaj

Cov tshuaj metabolic ruaj khov yog qhov tseem ceeb ntawm kev ua tshuaj. CES1 thiab CES2 muaj kev cuam tshuam loj heev thiab ib nrab - lub neej ntawm ester - cov neeg sawv cev. CES1, ua daim siab carboxylenesterase, cuam tshuam cov kev tshem tawm cov txheej txheem thiab ntshav. CES2, raws li lub plab hnyuv carboxylenesterase, feem ntau cuam tshuam rau thawj - dhau hydrolysis ntawm orally sectionistered tebchaw. Ntsuam xyuas seb cov enzymes no metabolize cov neeg sib tw pab ua kom ua kom zoo dua cov tshuaj thiab khoom xa tuaj.

Cov tshuaj tiv thaiv phenotyping nrog co enzymes

Cov tshuaj tiv thaiv phenotypingyog qhov tseem ceeb los txiav txim siab qhov tseeb enzymes lub luag hauj lwm rau cov tshuaj biotransformation. Ob Ces1 thiab Ces2 yog feem ntau koom nrog cov kev tshawb fawb no kom nkag siab txog lawv cov kev pab tshwj xeeb. Yog cov tshuaj phenotyping tuaj yeem qhia txog kev txhim kho ntawm prodrugs tsim rau kev ua kom los ntawm Ces1 lossis Ces2, ua kom cov tshuaj xa khoom thiab txhim kho cov tshuaj uas muaj peev xwm thiab hloov kho cov tshuaj.

Cov kws tshawb fawb siv cov CES) thiab cov kab mob Menboxyles (rau lub siab carboxyles (rau cov hnyuv ntxig rau kev ua haujlwm) ua cov tshuaj tiv thaiv hnyuv. Lub hom phiaj yog kom txo qis hloov pauv thiab ua kom paub tseeb tias cov kev metabolic yog zoo - cwj pwm.

CES enzyme inhibition thiab tshuaj siv - Yeeb yaj kiab

CES Enzyme Inhibitionyog qhov kev txhawj xeeb loj zuj zus vim nws lub peev xwm los ua rau cov tshuaj tseem ceeb - cov kev sib cuam tshuam. Inhibitalit CES1 tuaj yeem cuam tshuam cov metabolism ntawm nws cov substrates, ua rau cov tshuaj thiab tshuaj lom. Ib yam li ntawd, CI2 inhibition nyob rau hauv txoj hnyuv tuaj yeem txo cov kev ua kom muaj kev ua kom muaj kev ua tau zoo, txo qis kho kev ua tau zoo.

Ntau yam qauv tshuaj thiab kev tshuaj tsis zoo - Kev siv tshuaj yeeb tshuaj tam sim no suav nrog kev kuaj xyuas rau CES enzyme inhibition. Qhov no pab hauv kev twv xyuas cov chaw muag tshuaj ntawm cov chaw tshuaj tshiab thiab hauv cov tswv yim tsim kev siv tshuaj uas tsis muaj kev phom sij.

Piv txwv li, co - kev tswj hwm ntawm Ces1 inhibitor nrog metheschlephenidation tuaj yeem tsim cov tshuaj ntau ntawm cov tshuaj nquag, ua kom muaj kev pheej hmoo ntawm kev phiv. Ib yam li ntawd, CI2 inhibitionaps tuaj yeem cuam tshuam nrog kev ua kom lub tshuab hluav taws xob ua kom zoo, txo nws cov haujlwm anticancer.

Kev thov hauv cov kws tshawb fawb

Carboxylesteresase 1 (CES1) thiab Carboxylesterase 2 (CES2) tau ua cov cuab yeej tsis muaj nqis los hauv kev tshawb fawb niaj hnub. Lawv qhov tseem ceeb tshaj plaws:

• Kwv yees kev siv tshuaj metabolic ruaj khov.
• Kev ua cov tshuaj tiv thaiv phenotyping rau qhov tseeb enzyme daim phiaj.
• Soj ntsuam coes enzyme inhibition rau cov tshuaj muaj tshuaj - Cov kev sib cuam tshuam.
• Tsim CES - Ua haujlwm rau Prodrugs rau kev hloov kho.

Lub luag haujlwm ntawm Ces1 ua thawj daim siab carboxylenests thiab CES2 yog lub nroog loj ntawm carboxylests yog zoo - Los ntawm kev sib xyaw ua ke raug profiling rau hauv kev tsim tshuaj rau kev tshuaj siv tshuaj, kws tshawb fawb tuaj yeem tsim kev nyab xeeb dua thiab muaj txiaj ntsig zoo.

Tag

Hauv kev xaus, carboxylesteresase 1 thiab carboxylesterase 2 yog ntau tshaj li ntawm kev ua yeeb yam ntawm cov tshuaj ua thiab kev nyab xeeb. Qhov kev tsom xam ntawm CES1 (mob siab carboxylesase) thiab cov tshuaj yeeb tshuaj ua kom pom tseeb tias cov neeg sib tw ua yeeb yam kom zoo nkauj Ib txoj kev nkag siab tob ntawm CES muaj nuj nqi tsis tsuas yog kho kom muaj tshuaj tiv thaiv kev ua tiav tshuaj tab sis kuj pab tau kev ua tiav ntawm kev kho cov neeg ua haujlwm nkag mus ua lag luam.