Carboxylestserses (ces) mune zvinodhaka metabolism: maitiro echechi phenotyping uye DDI

Mazwi eKey: Drug - Dish Dishment (DDI), CarboxyleSteverese 2, Ces1, CessInal CarboxyleSerse, Ces enzyme Inhibition, Dish Metabolic Stabiles, Reaction phosotherping.

Chigadzirwa chefae

Nhanganyaya

CarboxylEresErases (ces) ndeye kiyi hydrolytic enzymes inosanganisirwa mune metabolism yehuwandu hwakawanda hwe esters - Uye Aride - Inayo Zvinodhaka. Pakati peizvi,Carboxylestserose 1 (CES1)uyeCarboxylestese 2 (CES2)ndivo vane mukurumbira muvanhu. Yavo yakasarudzika tishu yekugovera uye substrate chaiyo inoita ces1 uye ces2 cent centrain kune nzwisiso yezvinodhaka metabolism,Zvinodhaka metabolic kugadzikana, uyeMushonga - Kubata kwezvinodhakamune sesaceceucial sainzi.

CES1 uye CES2: Yemhando uye inoshanda musiyano

CarboxyleSteserase 1 (CES1) inoratidzwa zvakanyanya muchiropa uye inowanzotaurwa nezvayoChiropa chechifananidzo. Iyi enzyme inozivikanwa nekuda kweiyo yakajeka substrate chaiyo, metaboling madhiragi akadai saOseltamirir, methylphenidate, uye clopidog. Mukupesana, carboxylestese 2 (Ces2) inowanza zvakanyanya mumudumbu, saka zvinowanzodaidzwa kunziDhizaina carboxyleserse. Ces2 inotora basa rakarukwa mune metabolism reanticancer vamiririri saIrinothercan uye prodrugs akadai saCapecitabine.

Kutaura kusiyanisa kweCES1 uye CES2 kunovaita zvinangwa zvekutsoropodza muAdme (Kubata, kugoverwa, metabolism, uye kunyarara) profiltion. Zvese zviropa carboxylesserse (ces1) uye dumbu carboxyleserse (ces2) inoongororwa nguva nenguva yekudonha kwekutanga zvinodhaka.

Basa mune zvinodhaka metabolic kugadzikana

Drug metabolic kugadzikana chikamu chakakosha chePharmacokinetics. Ces1 neCes2 inokanganisa zvakanyanya kugadzikana uye hafu - hupenyu hwe ester - rine maratidziro ekurapa. Ces1, kuve chiropa chiropa kirivha, chinokanganisa systemic clearance uye plasma kuratidzwa. Ces2, seyakatarwa carboxyleereraSeverse, kunyanya kukanganisa yekutanga - Pass hydrolysis yemamiriyoni emuromo muromo. Kuongorora kuti ma enzyemes aya metabolize mumorekuru anobatsira anobatsira zvinodhaka uye kutumira.

Reaction phenototyping neCES enzymes

Reaction phenototypinginokosha kuti uone iyo chaiyo enzymes ine chekuita neBlueRansformation. Ose CES1 neCES2 dzinowanzobatanidzwa muzvidzidzo izvi kuti vanzwisise zvipo zvavo chaizvo. Kugadziriswa kwechokwadi phenotyping kunogona kuzivisa kukura kwe prodrug

Vatsvagiri vanoshandisa mari yekudzoreredza CES1 uye CES2 enzymes, chiropa carrosomes (yechifananidzo chechiratidzo chechiitiko), uye mumiriri microsomes (yemukati memucrosomesylasserera chiitiko) kuita zvakaringana kuita basa. Chinangwa ndechekuderedza kusiyana-siyana uye kuve nechokwadi chekuti metabolic nzira dzakapora - inoratidzirwa.

Ces enzyme inhibition uye zvinodhaka - kutaurirana kwezvinodhaka

Ces enzyme inhibitionIko kunetsekana kuri kuwedzera nekuda kwekugona kwayo kukonzeresa zvinodhaka - kutaurirana kwezvinodhaka. Inhibiting Ces1 inogona kukanganisa metabolism yeiyo substrate, inotungamira kune yakawedzera mishonga yezvinodhaka uye yehupfu. Saizvozvo, ces2 inhibition mumudumbu inogona kuderedza prodrug activation, kudzikisa maitiro ekurapa.

Mazhinji mishonga yekiriniki uye kiriniki Izvi zvinobatsira mukufungidzira iyo pharmacokinetic maitiro emasangano emakemikari mitsva uye mukugadzira nzira dzekutarisa dzinoderedza njodzi.

Semuenzaniso, CO - Administration yeCes1 Inhibitor ine methylphenidate inogona kusimudzira plasma plasma misheni yemushonga unoshandira, zvichishandisa njodzi yemhedzisiro yakaipa. Saizvozvo, Ces2 inhibition panguva yekubatanidza chomotherapy inogona kukanganisa activation yeIrinoterecan, achidzora chiitiko chayo anticancer.

Chikumbiro muMishonga Kutsvaga

CarboxyleSteverese 1 (CES1) uye carboxylestese 2 (CES2) yave zvishandiso zvisingabvumirwe mukutsvaga kwemazuva ano mishonga. Kukosha kwavo spans:

• Kufanotaura zvinodhaka metabolic kugadzikana.
• Kuitisa kuita phenototyping yechokwadi enzyme mepu.
• Kuongorora CES Enzyme Inhibition kuFefast Drug - Kubata kwezvinodhaka.
• Kugadzira CES - Activated pradrugs yeakavandudzwa kutumira.

Basa reCes1 seyekutanga chiropa carboxyleserselesterase uye ces2 seyenzvimbo huru yematanda emaraki mukarasi Nekubatanidza ces kunopupa mune zvinodhaka mapipi pipi, masayendisiti anogona kugadzira mishonga yakachengeteka uye inowedzera inoshanda.

Mhedziso

Mukupedzisa, carboxylestsersesterase 1 uye carboxyleverese 2 inopfuura kungoita chete metabolic enzymes-ivo vanokoshesesa vanoita zvinodhaka uye kuchengeteka. Iyo Cual inotarisa paCES1 (chiropa carboxylesersesterase) uye cessinal carboxylesterrase) mune zvinodhaka mrenoting Kunzwisisa kwakadzika kweCESS basa hakungori chete kufambisa dhizaini yezvinodhaka asi zvakare inowedzera huwandu hwekubudirira kwevamiriri vemitambo vachipinda mumusika.