Antibody - medicamento Conjugate (ADC) est relative novum genus biotechnology medicamento quod copulat parva molecule therapeutica componit ad targeting antibodies / antibody fragmentum in linkers. Hoc coniugatio non solum augendae medicamento stabilitatem tum targeting accurate, sed etiam reducere orci toxicity et latus effectus, ergo improving medicamento scriptor medicinales index. Una Maior commodum ad ADC est quod habet therapeutica effectus ad traditional parva molecule medicinae et specifica antibody, ita maxime propter targeted anti - tumor curatio.
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1.Structural compositionem ADC
Adc consistit ex tribus partes: antibody / Antibody fragmentum, Linker et parvum moleculae compositis. In antibody parte est plerumque potest esse endocytosed: eius principalis munus est ad mediam antibody - dependens cell phagocytosis in target modo. Et Linker sit stabilis satis ad circulationem ad sustinere medicamento ex degradation vel saltem minimize degradation priusquam ad target organum. Post intrantes in scopum organum, activae parva molecule componit sunt celeriter dimisit ad producendum pharmacodynamic effectus in scopum cellulis.
Post ADCS Intra corpus, possunt obligare antigens super superficiem scopum cellulis cum ductu Monoclonal elementorum et ulteriores transferantur in scopum cellulis. Post ostium in cellulis (maxime in lysosomes) ADCs potest dimittere parva moleculae toxins vel toxin analogs (i.e. effectrix moleculis) per eget / enzytmatic actio est "occiditis" scopum cellulis. Licet ADCs miscere commodum de altum specifica de Monoclonal antibodia et fortis cytotoxicity parva moculari toxins, etiam adducere plures provocationes suas pharmacipinetic investigationis.
Fig I ADC medicamento structure
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2.Pharmacokinetic Desertistics de ADC
Cum de Molecular pondus et localis volumen, antibody maxime constituit AdC structura. In generali, ADC exhibet multis pharmacokinetic characteres similes his antibody se. Tamen, quia ADC est compositum ex III moleculis, praesentia et distributionem cuiusque pars, una cum suis metabolitarum, opus ad investigandum eodem tempore.
Igitur pharmacoginetics studium ADC est difficilius quam traditional anti - tumor medicinae, phaenomenon maxime reflectitur in effusio, distribution, metabolismi et excretion (adme) processus. ADC est administratum per iniectio, ita eius distribution est similis, ut antibody medicamento. Specie distribui antigensis in textuum cum magna volumina sanguinis, ut iecoris, renibus et aliis organis. Iecoris est maxima medicamento metabolizing organum in humano corpore. Ut ADC intrant lysosome (vel acidified iecoris homogenate), ad toxicus effectus parva moleculo component et pharmacological metabolitarum dimisit ex ADC et metabolized in Cytochrome P450 in iecur in P450 in iecoris P450. Concurrenter medicamento - medicamento commercium inde ex enzyme inductione vel enzyme inhibitionis potest etiam fieri.
Ultimately, post metabolismi ad ADC, quidam liberum effectrix parva moleculis, parva moceular pondus peptides, amino acidum - coniunctum effectionor moleculis, et parva in faeculatas in glomerularibus et transporter mediante.
Fig II muneris mechanism ADC pharmaca
(Source Pharm peccatum B. MMXX Sep; X (IX) MDLXXXIX - MDC)
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3 "unus - subsisto" solution in - vitro studio ADC
The Technical Guidelines for Non-clinical Research of ADC issued by Center for Drug Evaluation (CDE) puts forward relevant requirements on the research strategy and basic framework of ADC study in non-clinical stage, and emphasizes the necessity of in-vitro and in-vivo studies on pharmacological mechanism and pharmacodynamic effects of ADC.
Ut in occursum in customers 'necessitates ad mane in - vitro studiis ad ADC in non - C. Clinical scaena, Iphase, ut a duce in Biological Reagents in - Vitro Studies Studies. Nam progressionem ad ADC, primus gradus est determinare specifica forma payload release, et plerumque in - vitro payload s9 fraction, lysosomal elit, acidified hepatis homogenate vel target cellulis. Secundo, ad oratio ad complexu pharmacokinetic characteres de ADC, Iphase habet developed integram range of multi - genus, multi - classis et multi - organum adme products ad teloneariorum ad eligere ad suscipere initial protegendo de medicamento metabolismi.
Obsequium
Products adeptus ex officialis fontes cum patet, traceable origines.
Salus
Animalia probata pro infectiosis agentibus ut productum qualis et salus.
Sublimitas
Cell pura potest pervenire super XC%.
Princeps viability
Cellula viability potest pervenire super LXXXV% ad occursum mos necessitates.
Alta recuperatio rate
Frigidus Recuperatio rate potest excedunt XC%.
PROBUS
Non possumus providere customized servitium pro raris speciei et textuum secundum Lorem scriptor specialis necessitates.
Infra est a album of quidam Iphase scriptor products.
Genera |
Classificationes |
FRAGMENTUM |
Lysosome iecur |
Acidified iecoris homogenate |
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Iecur / intestinis / renes / pulmones Microsomes |
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Iecur / intestinorum / renibus / pulmonis S9 |
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Iecur / intestinorum / renibus / pulmonis Cytoplasmic fluidum |
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Prima Hepatocyte |
Suspensus hepatocytes |
Hepatocytes |
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Recombinant enzyme products |
Cype recombinase |
UGT Recombinase |
Post tempus: MMXXIV - IV - XVI 15:08:41