Wuhan Demeikai Biotechnology Co., Ltd
返回首页 | 加入收藏 | 设为首页
Wuhan Demeikai Biotechnology Co., Ltd
whatsapp:+86 18942921723(Ms.Gao) 
+86 13260607296(Mr.Wang)
Vc-MMAE powder Home您现在的位置:HOME >> PRODUCTS >> Inhibitors

Vc-MMAE powder

所属类别:Inhibitors 点击次数:904次 发布时间:2017-05-18

Vc-MMAE powder
 Vc-MMAE Basic Info.
Synonyms:Maleimidocaproyl-valine-citrulline-p-aminobenzoyloxycarbonyl-monomethyl auristatin E; Vedotin
VcMMAE, Maleimidocaproyl-valine-citrulline-p-aminobenzoyloxycarbonyl-monomethyl auristatin E, Vedotin
Molecular Formula:C68H105N11O15
Molecular Weight:1316.63
CAS Registry Number:646502-53-6
Antibody-drug conjugates (ADCs) require thorough characterization and understanding of product quality attributes. The framework of many ADCs comprises one molecule of antibody that is usually conjugated with multiple drug molecules at various locations. It is unknown whether the drug release rate from the ADC is dependent on drug location, and/or local environment, dictated by the sequence and structure of the antibody carrier. This study addresses these issues with valine-citrulline-monomethylauristatin E (vc-MMAE)-based ADC molecules conjugated at reduced disulfide bonds, by evaluating the cathepsin B catalyzed drug release rate of ADC molecules with different drug distributions or antibody carriers. MMAE drug release rates at different locations on ADC I were compared to evaluate the impact of drug location. No difference in rates was observed for drug released from the VH, VL, or CH2 domains of ADC I. Furthermore, four vc-MMAE ADC molecules were chosen as substrates for cathepsin B for evaluation of Michaelis-Menten parameters. There was no significant difference in KM or kcat values, suggesting that different sequences of the antibody carrier do not result in different drug release rates. Comparison between ADCs and small molecules containing vc-MMAE moieties as substrates for cathepsin B suggests that the presence of IgG1 antibody carrier, regardless of its bulkiness, does not impact drug release rate. Finally, a molecular dynamics simulation on ADC II revealed that the val-cit moiety at each of the eight possible conjugation sites was, on average, solvent accessible over 50% of its maximum solvent accessible surface area (SASA) during a 500 ns trajectory. Combined, these results suggest that the cathepsin cleavage sites for conjugated drugs are exposed enough for the enzyme to access and that the drug release rate is rather independent of drug location or monoclonal antibody carrier. Therefore, the distribution of drug conjugation at different sites is not a critical parameter to control in manufacturing of the vc-MMAE-based ADC conjugated at reduced disulfide bonds.

上一产品: Buy Drostanolone Enanthate powder
下一产品: Buy Calicheamicin y1 powder for research only
友情链接:made-in-china | 西地那非原料药 | 伐地那非原料药 | 他达那非原料药 | 
Copyright © 2004-2015 Wuhan Demechem Bio-tech Co., Ltd All Rights Release all
whatsapp:8618942921723 Company address: wuchang district in wuhan city, hubei province austral soho north 4 1 unit。
  • QQ咨询

  • 电话咨询

  • 13260607296