A cikin Kabarin Ciwon Ciwon Muryar Indicring

Keywords: ATP -, Cassette Cassette (ABC), ABC Sadarwa, MDR1, METP1B1, MEP II, ICH1, BCRP, Caco, IC - Hek293 MOck, mai ɗaukar hoto SLC.

Kayayyakin iphayan

Baya

A cikin Account Aikace-aikace Marasa Yi Amfani da kwayoyi da yawa lokaci guda, kuma waɗannan magunguna suna haifar da magani) hulda miyagun ƙwayoyi (DDI) waɗanda ke da damar haifar da mummunar cutar. Gwajin DDI yawanci yana farawa da gwajin Vitro don gano abubuwan da ake samu da ƙwayoyin DDI da kuma samun sigogi na Ciniki don ƙarin nazari. Magungunan miyagun ƙwayoyi sun daɗe sun dade da binciken binciken DDI. A cikin 'yan shekarun nan, tare da ci gaban fasahar kwayar halittar kwayoyin halitta, an ci gaba mai ci gaba a cikin binciken magunguna na vitro, da mahimmancin kimantawa na tushen sufuri na masu sufuri.

Sufuri da aikinsu

Masu jigilar kaya na nufin sunadaran transmetrest na sel nmbrane na kyallen takarda daban-daban waɗanda ke sulhu da abubuwan da ke tattare da abubuwan da suka dace. A cikin jigilar kwayoyi na vitro babban lokaci ne don sunadarai waɗanda ke ɗaukar magunguna kamar yadda ke stremranes, sun wanzu membrest magunguna, akasin su da iyalai biyu: da ATP - Makonds kaset (ABC)Superfamily da Siferin Solin SuperFamily (SLC sufuri), wanda ya mamaye tsarin jigilar magani na transmbrest magani.

ABC sufurisune ATP - Masu ba da gudummawa waɗanda ke motsa su na zamani (misali, ions, lipsids, da kwayoyi) a kan membranes na taro. Suna wasa mahimman matsayi a cikin juriya da magani, metabolism, da detloxificationlultification.Sojojin SLCYawancinsu na sakandare suna aiki ko masu tallafawa waɗanda ke sulhu da motsi kamar glucose, amino acid, da neurotransmters. Ba kamar sufurin ABC ba, ba sa buƙatar ATP kai tsaye amma dogara da gradial na ion.

Masu sufuri da ke yin sulhu da magunguna sun hada da P - Glycoprotein (PA - GP), ko Multi juriya na 1 (BCR1), cutar kansa ta nono (BCRP). Su ne membobin ATP - Hinding Cassette (ABC) dangi mai jigilar kaya (ABC) suna amfani da ƙarfin hydrolyzed ATP don jigilar magunguna da abubuwa masu kyau. Masu sufuri da ke sa hannu kan shigowar magunguna a cikin sel na iya ɗaukar sakamako zuwa ga shafin yanar gizon da zasu yi aiki (Oatps), jigilar kayan jigilar kayayyaki (Oatps), jigilar kayan aiki (OATS), jigilar kwayoyin cuta (OctS), da sauransu.

Motar kayayyaki da aikinsu:

• -Bansp(Bile firijin firidin):Mai matukar muhimmanci ga bile acid a hanta, BSP dysfunction yana da alaƙa da cutar choleestics ta hanta. Magunguna - Haƙiƙa -- BSET na iya haifar da hpatotoxicity.
• -BCRP(Jin cutar kansa ta nono):BCRP yana shafar ƙwayar ƙwayar cuta da etants, fitarwa da substrates daga sel da jini suna ɗaukar ciki.
• -Mate1 / ME2 - K(Motidrugug da kuma Toxin Estrussion sunadarai):Located a cikin Hegal da Hepatic kyallen, Mataki da ME2 da MEPREGSE CSIC, masu aiki da kwayoyi tare da yin sulhu na renal.
• -Oatop1B1(Slco1b1):A hepatic Uptake Sirrin Mahimmanci mai mahimmanci ga Contin Cire. Oatopb1 taka muhimmiyar rawa wajen magance matsalar mahaɗan da ke da kwayoyin cuta irin su, da kuma hepirubs, antroals, da magunguna na anticaler, da magunguna na anticaler, da magunguna na anticaler, da magunguna na anticaler, da magunguna na anticaler, da magunguna na anticaler, da magunguna na anticaler, da magunguna na anticaler, da magunguna na anticaler, da magunguna na anticaler, da magunguna na anticaler, da magunguna masu tursasawa.
• -Oat1(Slc22a6):Yana ba da sulhu na koda, gami da rigakafi da NSAIDs, tasiri nephrotoxicity hadarin hadarin.

Inshorar sufuri da DDI

Hanawawani muhimmin bangare ne na ci gaban kwayoyi. Intiphions na jigilar kaya yana taka muhimmiyar rawa a cikin miyagun ƙwayoyi - Cikakkun hanyoyin miyagun ƙwayoyi (DDI) ta hanyar shafar sha, rarraba, da kuma expo labari, da kuma exxtrectionsm. Harshen sufurin jigilar kayayyaki kamar MDR1 (P - GP) da BCRP na iya rage fasahar sel. Hakazalika, hana masu jigilar kayan maye kamar Oatp1B1 na iya rage cire magani, yayin da ke BSep. Bugu da ƙari, sufuri kamar aure1, ME2 - K, da Oat1, waɗanda ke da mahimmanci a kawar da cutar magani da gudummawa, za a ba da gudummawa ga tara magani. A cikin samfuran vitro, ciki har daMdck iidaCaco - 2Lines na sel, ana amfani da su sosai don kimanta waɗannan ma'amala na sufuri, yana samar da kyakkyawar fahimta cikin yuwuwar dDI yayin ci gaban magunguna.

A cikin samfuran Vitro don karatun sufuri

Gwaji aikin sufuri da kuma ƙaddara aiki - Adadin DDIs dogara da ƙwararrun samfuran tantanin halitta. Masu bincike suna amfani da suHek293 mocksel a matsayin mummunan iko, tabbatar da cewa duk wani abin da aka lura dashi shine saboda takamaiman mai aiki. MOCK yana ba da daidaitaccen abu, yayin da Hek293 mock ya kasance tsakiya don tabbatar da ingancin gwaji. Hanya ɗaya tana aikimembrane vesiclesDaga ƙwayoyin sufuri na wuce gona da iri, galibi ana ware daga sel na hek293. Hakazalika,Mai ɗaukar hoto SLCModel suna da mahimmanci don rarrabe takamaiman aikin sufuri daga rashin daidaituwa. MOCK SLC sufuri a tabbatar da cewa lura da substrate motsi shine mai jigilar kayayyaki - dogaro, da kuma yin gwajin jigilar kayayyaki slc Saduwa da samfurin. Wannan kusantarwar ta amfani da Hek293 MOck da MOVOL SLC Siyarwa Inganta ikonmu na nazarin ATP - Sufuri mai dogaro da tsangwama daga sararin samaniya.

Caco - 2 layin layi, wanda aka samo daga Carcinoma na mutum, wani yanki ne na daidaitaccen samfurin da ake amfani da shi don kwaikwayon shaukar ƙwayoyin cuta. Ikonsa na bambance a cikin shigarwar - Kamar ƙwayoyin sel da yawa - kamar p - gp da bcrp-yana sa shi mahimmanci don tantance ƙwayoyin cuta na biyu.

Bugu da ƙari, mai jigilar kayayyaki - takamaiman samfurori kamar sel na BCRP na ɗan adam yana ba da bincike na substrate, da kuma irin halayen jigilar magunguna, da kuma gwargwadon abin da ke hana su aiwatar da ayyukan sufuri. Idan aka haɗu da bayanai daga bayanai daga amsawar vesicular, waɗannan tsarin salula suna ba da cikakkiyar fahimta cikin ƙarfin jigilar kaya - Areedungiyoyin miyagun ƙwayoyi.

Ƙarshe

A taƙaitawa, fahimtar ma'amala da sufuri yana da mahimmanci don inganta amincin magani da inganci. Masu sufuri kamar MDR1 (P - GP), BCRP, da BCRP, da BCRP tare da masu jigilar kayayyaki kamar Oatp SL1 Silital Properinger Mahimmanci Mahimmanci Mahimmanci. Yin amfani da samfurin Vitro ciki har da MDCK II, Caco - 2, BCRP na ɗan Adam na samar da doguwar ma'amala da magunguna da kuma zubar da miyagun ƙwayoyi. Wadannan fahimta suna da mahimmanci don inganta ingantaccen magani da aminci a cikin saitunan asibiti.