Sulfotransferase (sult) rau DDI kev tshawb fawb, metabolic stability, thiab enzyme inhibition

Key words: drug-drug interaction (DDI), sulfotransferase (SULT), enzyme inhibition, SULT metabolic, metabolic stability, human SULT1A1 enzyme, human SULT1A3 enzyme, human SULT1B1 enzyme, human SULT1C2, human SULT1C4 enzyme, human SULT1E1 enzyme, human SULT2A1 enzyme

1 Iphase tsim

2 enzymatic kev tshawb fawb hauv kev tsim kev tshuaj

Hauv kev siv tshuaj, kev kawm ntawm kev ua yeeb yam ntawm cov khoom siv metabolic thiab enzyme inhiboles ntawm metabolic enzymes xws li cy450, ugt, sult, etc. yog qhov tseem ceeb heev. Kev tshawb fawb txog kev tshawb fawb txog kev siv vitoype, thiab ntsuas cov kev cuam tshuam rau cov gene polymorphism rau cov tshuaj kho tus kheej. Enzyme inhibition kev tshawb fawb tsom rau ntawm cov tshuaj inhisitic cuam tshuam los ntawm cov yeeb tshuaj lossis sib xyaw ntawm cov tshuaj metabolic (ircersible inhibition), ntsuas qhov ntsuas IC50 / KI los twv sebKev Siv Tshuaj - Yeeb Tshuaj (DDI)kev pheej hmoo. Cov kev tshawb fawb no muab cov tshuaj scientific rau kev tsim kho yeeb tshuaj, xws li txheeb xyuas cov tshuaj lom neeg lom zem), thiab kev qhia txog cov tshuaj muaj kev ntsuas. Cov kev sib tw tseem ceeb nyob rau hauv kev hloov pauv ntawm hauv Vivo rau hauv Vivo cov ntaub ntawv thiab kev kuaj pom ntawm cov metabolites tsawg heev. Nyob rau hauv lub neej yav tom ntej, cov qauv qib siab xws li cov orgoids tuaj yeem siv los txhawb kev tshawb fawb ntxiv.

3 Sulfotransferase (sult)

Sulfotransferase (sult)yog ib hom kev hloov pauv uas catalyzes hloov chaw sulfate thiab yog koom nrog cov tshuaj hormones (xws li cov tshuaj hormotransmitting) thiab exogenous tebchaw (xws li tshuaj thiab ib puag ncig cov pa paug). Sulfotransferases feem ntau yog nyob rau hauv cytoplasm thiab golgi apparatus, muaj kev koom tes ntawm cov tshuaj me me (xws li cov tshuaj hormeculation) thiab cov roj ntsha li, lipids, glycosaminoglycans). Sulfotransferases tau txheeb xyuas kom muaj ntau subtypes, feem ntau yog suav nrog sult1, Sult2, thiab Sult4. Ua haujlwm tsis zoo ntawm SulfotRanserase tuaj yeem ua rau kev siv tshuaj yeeb txawv txav, mob cancer, endocrine disorders, thiab neurological disciters.

4 sulfation / sulfonation metabolism

Sulfonation metabolism (tseem hu ua cov metabolation Tib neeg SulfotTsite (tseem hu ua sulfatase) muaj ntau yam ntawm cov substrates hauv lub cev, feem ntau faib tawm hauv plab hnyuv siab muag xws li daim siab, plab hnyuv, raum, thiab lub ntsws. Cov tib neeg muaj xws liSult1a1, Sult14a3, Sult1b1, Sult1c2, thiabSult1c4 (Cov lus 1). Rau feem ntau substrates, Sulfoterase me me metabolism feem ntau cov khoom ua pov thawj substrate inhibition cov yam ntxwv; Tsawg cov theem siab cov kev hloov siab feem ntau ua rau muaj enzyme ua rau hais tawm.

Cov lus 1 Qhov faib tawm thiab ua haujlwm ntawm ib feem ntawm cov sult superfamily hauv tib neeg lub cev

5 Qhov tseem ceeb cov ntawv thov ntawm sult kev txhim kho

5.1 Hauv kev ntsuam xyuas vitro ntawm DDI raws li cov metabolism

Cov hauv kev ntsuas vitro sult datiated DDI yog tsuas yog nqa los ntawm kev xaiv tshuab hluav taws xob hauv tib neeg hepatic cyosplasm lossis cov qauv xov tooj ntawm tes qhia tshwj xeeb subtyples. Kev tsim qauv feem ntau suav nrog:

Kev Ntsuam Xyuas Cov Khoom Siv Hluav Taws Xob: QuatifyA tus nqi ntawm sulfated metabolite tiam los ntawm LC - MS / MS / MS thiab xam cov nqi Inhibition (IC50 / KI).

Cov kev ua yeeb yam kev pheej hmoo kev pheej hmoo: Yog tias inhibitor tseem ceeb txo cov tshuaj metabolite (inhibition tus nqi

5.2 sult metabolic kev kawm ruaj khov

Hauv kev siv tshuaj yeeb, kev kawm ntawm sultetcholic ruaj khov yog ua los ntawm cov vitro incubation (hepatic sulfation tus nqi ntxiv, ntsuas cov qauv metabolic kev phom sij, thiab cov qauv kev kho mob.

5.3 metabolic substrate

Txoj kev tshawb fawb substrate (metabolic pathwifications tus qauv) ntawm cov tshuaj lom neeg siv tau ncaj qha rau cov neeg siv tshuaj tiv thaiv kab ntsig, thiab tom qab ntawd txheeb xyuas cov khoom siv can kom haum, thiab tom qab ntawd ua rau lawv cov neeg ua haujlwm sib koom tes thiab laij lawv cov kev sib koom ua ke.

Lub hauv paus ntsiab lus tseem ceeb thiab kev ua haujlwm ntawm cov tshuaj txwv tsis pub muaj tshuaj lom neeg lossis cov metabolite ntau lawm arecetin thiab dcnp ntawm sultional hauv tib neeg hepatic cytoplasm system.

5.4 enzyme inshibition kev tshawb fawb

Sult yog koom nrog hauv cov metabolism ntawm ntau cov tshuaj endogenous thiab yeeb tshuaj. Yog tias muaj cov tshuaj tau tsim kom muaj kev ua haujlwm ntawm Sult, tej zaum yuav muaj teeb meem kev nyab xeeb thaum sib faib tshuaj. Lub ntsiab lus tseem ceeb thiab kev ua haujlwm ntawm Sult enzyme inhibition los ntawm kev ntxiv cov tshuaj ntshiab enzyme yog los ntawm kev ntxiv cov tshuaj ntshiab thiab kev sojntsuam xws li p - nitrophenol.

6 qhov xaus

Sulfotransferase (sult) ua lub luag haujlwm tseem ceeb hauv tshuaj metabolism (yeeb tshuaj (DDI), thiab kev ntsuas kev nyab xeeb. Cov sulfation metabolism kev kho kho los ntawm nws cuam tshuam cov tshuaj tiv thaiv tshuaj, ua kom muaj kuab paug tshuaj thiab lom neeg cov kev pheej hmoo pheej hmoo. Los ntawm kev sib txuas ua ke hauv cov qauv vitro (mob siab rau cov khoom) nrog LC - MS / MS / MSUMOLOGSE, cov kev ua kom zoo nkauj, cov tshuaj kho mob. Nyob rau hauv lub neej yav tom ntej, cov qauv qib siab xws li cov kev mob effoids yuav txuas ntxiv cov txheej txheem kev tshawb fawb ntxiv rau cov kev ntsuas kev ruaj khov thiab kev nyab xeeb rau kev tsim kev nyab xeeb thiab kev nyab xeeb hauv kev tsim kev nyab xeeb.

Phau ntawv

Li, Y., Lindsay, J., Wang, L. L., & Zhou, S. (2008). Cov qauv, muaj nuj nqi thiab polymorphism ntawm tib neeg cytosolic sulfotranserases. Tam sim no cov metabolism tam sim no, 9(2), 99 - 105.