Chimodzi - siyani malonda: yankho la mu - Vitro Adc Kafukufuku

Antibody - conjugate (ADC) ndi mtundu watsopano wa biotechnology mankhwala omwe amamwalila ang'onoang'ono amagwiritsa ntchito ma antibodies / matenda a anibon. Izi sizimangokhala kukhazikika kwa mankhwala osokoneza bongo komanso kuwongolera kulondola, komanso kuchepetsa kuwopsa kwa matenda ndi zotsatira zoyipa, chifukwa chake kukonza njira zochizira za mankhwala. Ubwino umodzi wa ADC ndikuti ili ndi zochizira zazing'onoting'ono ndi mankhwala a Molecuta a Molecule ndi mawonekedwe a antibrody, motero amagwiritsidwa ntchito makamaka chifukwa chokana anti - chithandizo chotupa.

1. 1. Kupanga kwa ADC

ADC imakhala ndi magawo atatu: antibody / antibody, anker, ndi molekyulu yaying'ono. Gawo la antibody nthawi zambiri limatha kukhala litayi: Ntchito yake yayikulu ndi yoyimira antibody - cell ya phagocytosis m'njira yochokera. Linker iyenera kukhala yokhazikika yoyendetsedwa ndi mankhwalawa kuwonongeka kapena kuchepetsa kuchepa kwa chiwalo chisanafike. Pambuyo polowa chiwalo chandamale, mankhwala ang'onoang'ono a molekyulu amatulutsidwa mwachangu kutulutsa pharmacondynamic zotsatira pa maselo a Dera.

Adcs pambuyo pa thupi, amatha kumanga ma argnerans pamtunda wa maselo omwe akutsutsana ndi chitsogozo cha ma antibododies awo ndipo amasamutsidwanso m'maselo a Dera. Pambuyo polowera m'maselo (makamaka mkati mwa lysosomes), Adcs amatha kumasula ma boleks ang'onoang'ono (I.E.E.E.E. Ngakhale madc amaphatikiza phindu la ma antibodol antibodies ndi cytotoxicity wa poizoni wawung'ono wambiri, amabweretsanso zovuta zambiri kwa kafukufuku wa phar pharmacokinetire.

Mtundu 1 ADC

2. 2.pharmacokinetic mikhalidwe ya ADC

Ponena za kulemera kwa ma celecular ndi voti yaying'ono, antibody imapanga mawonekedwe a ADC. Mwambiri, ADC imawonetsa zinthu zambiri za pharmacokinetic ofanana ndi antioni. Komabe, chifukwa Adc ndi kuphatikiza kwa mamolekyulu atatu, kupezeka kwa chinthu chilichonse, limodzi ndi metabolites, ayenera kusanthulidwa nthawi yomweyo.

Chifukwa chake, kafukufuku wa pharmacokinetics kuphunzira kwa ADC kumakhala kovuta kwambiri kuposa anti - chotupa cha chotupa, chotupa chimawonetsedwa mu mayamwidwe, kagayidwe kake (ADMEbolism. ADC imaperekedwa ndi jakisoni, chifukwa chake kugawa kwake kumafanana ndi mankhwala a antibody. Amagawidwa mwachindunji kwa ma antigens mu minofu yokhala ndi magazi akulu, monga chiwindi, impso ndi ziwalo zina. Chiwindi ndi chiwalo chachikulu kwambiri chosokoneza thupi m'thupi la munthu. Monga ADC Lowani lysosome (kapena acidheed homogenite), zoopsa za mankhwala ang'onoang'ono a Moleklulological zimamasulidwa kuchokera ku ADC kenako ndikukakamizidwa ndi etrochrome P45Mme mu chiwindi. Nthawi yomweyo mankhwala - kulumikizana ndi mankhwala osokoneza bongo chifukwa cha enzyme polection kapena enzyme zoletsa.

Pamapeto pake, pambuyo pa kagayidwe ka ADC, ma molekyulu amasulukidwe ang'onoang'ono, amino acid - mamolekyulu olumala, komanso zidutswa zowongoka za metabolic zitha kufesa.

Mkuyu 2 Magwiritsidwe Abwino Mankhwala a ADC

(Source: Acta pharm Tchimo B. 2020 Sep; 10 (9): 1589 - 1600)

3. 3. "imodzi - Imani" Njira Yothetsera - Vitro Phunziro la ADC

Malangizo aukadaulo kwa Wopanda - Kafukufuku wa ADC omwe amafunsidwa ndi mankhwala osokoneza bongo (CDRO)

Pofuna kukumana ndi zosowa za makasitomala oyambira - Maphunziro a Vitro a ADC mu ONT ON - Iphase, Onetsani " Pakukula kwa ADC, gawo loyamba ndikuwonetsa mawonekedwe ake omasulidwa, ndipo nthawi zambiri ku - Vitro Plaction Sertiction S9 Craction, acid Hepageni National kapena ma cell. Kachiwiri, kuthana ndi mankhwala osokoneza bongo a ADC, genfase yakhala ndi mitundu yonse yamitundu yokwanira - Kalasi ya Adme -

Kukhutisidwa

Zogulitsa zimapezeka kuchokera ku magwero ovomerezeka ndi zoyambira zomveka bwino.

Chitetezo

Nyama zimayesedwa kwa othandizira opatsirana kuti awonetsetse kuti ndi chitetezo komanso chitetezo.

Kuyera Kwambiri

Chiyero cha foni chimatha kupitilira 90%.

Kukula Kwambiri

Kusintha kwa maselo kumatha kupitilira 85% kuti akwaniritse zosowa za makasitomala.

Muyeso wobwezeretsa kwambiri

Mlingo wobwezeretsa umatha kupitirira 90%.

Zotheka

Titha kupereka chithandizo chamachitidwe m'malo mwa mitundu ndi minyewa yolingana ndi zosowa zapadera za makasitomala.

Pansipa pali mndandanda wa ena a zinthu za Iphase.