Mumwe - STOPTER Chigadzirwa: Solution yeIN - Vitro ADC Kutsvaga

Antibody - Doll Conjugate (Adc) rudzi rutsva rwezvinodhaka izvo vakaroora madiki madiki ekurapa anenge achiisa antibodies / Antibody Fragment. Uku kubatana hakugone kungowedzera kugadzikana kwezvinodhaka pamwe nekuvanzika kurongeka, asi kuderedza kiriniki chivharo uye mhedzisiro, saka kuvandudza zvinodhaka maratidziro. Imwe mikuru yeADC ndeyekuti ine maratidziro ekurapa kune mishonga madiki madhiragi emamolecule uye chaiyo yemanyokisi, saka inonyanya kushandiswa kurambidzwa kunamatira - bundu rekutapira.

1. 1.Rudzi rwekuumbwa kwe adc

Adc ine zvikamu zvitatu: Antibody / Antibody Fragment, Linker, uye diki molecule compound. Iyo Antibody chikamu chinowanzo kuve neyecycytosed: Basa rayo guru ndeyekurevesa antibody - Inotsamira Cell phagocytosis muchimiro. Iyo linker inofanirwa kuve yakagadzikana zvakakwana kuti utsigire zvinodhaka kubva mukushatiswa kana kuti zvinyoronyoro kusvibiswa usati wasvika pane chinangwa chechinangwa. Mushure mekupinda mucherechedzo wezvinangwa, madiki madiki madiki anokurumidza kuburitswa kuti abudiswe eharmacodynamic mhedzisiro pamasero ematare.

Mushure mekunge adss inopinda mumuviri, ivo vanogona kusunga kune zvimedu pamusoro pemasero ematare ane nhungamiro yeiyo monoclonal antibodies uye inoenderera mberi yakaiswa mumasero emanyowa. Mushure mekupinda mumasero (kunyanya mukati meLysosomes), Adcs inogona kusunungura madiki moliins toxins Kunyangwe ADCS ichisanganisa mukana wekusarudzika kweMonownal Antibodies uye kushatisa kwakasimba kwemanyorerwe madiki madiki, vanounzawo matambudziko mazhinji kune yavo yePermacokinic yekutsvaga.

Fig 1 Adc zvinodhaka chimiro

2. 2.Purrmacokinetic hunhu hweADC

Panyaya kune mamorekuru uremu uye spatial vhoriyamu, antibody inonyanya kuumba iyo adc chimiro. Kazhinji, Adc inoratidza akawanda mishonga yePharmacokinetic akafanana akafanana neayo emidhiya pachayo. Nekudaro, nekuti Adc isanganiswa yemamorekuru matatu, kuvapo uye kugovera kwechikamu chimwe nechimwe, pamwe chete nacho metabolites, inoda kuferefetwa panguva imwe chete.

Naizvozvo, iyo pharmaciki yekudzidza yeADC yakaomesesa zvakanyanya pane zvechinyakare anti - bundu rinodhaka, chiitiko chinonyanya kuratidzwa mukupinda, kugoverwa, methelission (admeton) maitiro. ADC inotumirwa ne jection, saka kugoverwa kwayo kwakafanana neiyo yemishonga yeanoshanda. Ivo vanogovaniswa zvakananga kune maAntigens mumatisiki ane huwandu hwakakura hweropa, senge chiropa, itsvo uye dzimwe nhengo dzevamwe. Chiropa ndicho chiumbwa chikuru chinodhaka mishonga mumuviri wemunhu. AS adc isa iyo lysosome (kana acidified chiropa homogenate), iyo ine chepfu madiki meturinele chikamu uye pharmacological metabolites inoburitswa kubva kuADC uye yakazotumbuka neiyo cytochrome P450 enzyme mune chiropa. Concurrenly drug - Kubata kwezvinodhaka kunokonzeresa kubva ku Enzyme kuwedzeredza kana enzyme inhibition inogona kuitikawo.

Pakupedzisira, mushure mekunge metabolism yeADC, mamwe magetsi madiki madiki mamorekuru, amino acid -

Fig 2 inoshanda Mechanism adc zvinodhaka

(Source: Acta Pharum Sin B. 2020 Sep; 10 (9): 1589 - 1600)

3. 3. "mumwe - STOP" mhinduro mu - vitro kudzidza kwe adc

Nhungamiro dzehunyanzvi dzeNon-Clinical kutsvagurudza kuongororwa kweADC yeVanoda

Kuti tisangane nezvinodiwa zvevatengi zvekutanga Zvekuvandudzwa kwe adc, nhanho yekutanga ndeyekuti uone chimiro chaicho chekusunungurwa, uye kazhinji musicload sisitimu yeHephiction S9 chidimbu, Lysosomal nharaunda, acidified hematic homogenate kana chinangwa chemasero. Kechipiri, kugadzirisa iyo yakaoma pharmacokinetic maitiro eADC, Iphose yakagadzira huwandu hwakakwana hwehuwandu - genus, kirasi - organe - organe -

Kutevedzera

Zvigadzirwa zvinowanikwa kubva kune zvematareji masosi ane akajeka, anoteedzera mavambo.

Kuchengetedzwa

Mhuka dzinoedzwa kune dzinotapukira vamiririri kuve nechokwadi chechigadzirwa mhando uye kuchengetedzwa.

Kuchena kwakanyanya

Kuchena cell kunogona kusvika pamusoro pe90%.

Yakanyanya Kuwanda

Cell vibility inogona kusvika pamusoro pe85% kusangana nevatengi zvinodiwa.

Yakanyanya Kudzorera Rate

Dzora rekudzora rate rinogona kupfuura 90%.

Inobatsira

Isu tinogona kupa yakagadzirirwa sevhisi yemhando isina kujairika uye tishu zvinoenderana nezvinodiwa zveVatengi.

Pazasi pane runyorwa rweimwe yezvigadzirwa zveIfese.