NOVEL CAMPTOTHECIN DERIVATVES AS ANTIBODY-DRUG CONJUGATES (ADC) PAYLOADS
摘要:
The present invention describes novel camptothecin derivatives and methods for preparing camptothecin derivative payloads bearing a linker with a functional group that can be used for conjugation to cell binding agents to generate cytotoxic drug conjugates. The present invention further relates to antibody drug conjugates made with camptothecin derivative payloads bearing a linker moiety conjugated to tumor associated antigen (TAA) antibody, preparation methods, pharmaceutical compositions and uses thereof for the treatment of cancer. Methods relating to the use of the novel ADCs to treat antigen positive cells in cancers and immunological disorders are also provided herein.
Synthesis and biological evaluation of neoglycosphingolipids
作者:Shuihong Cheng、Peixing Wu、Jing Han、Yiren Wang、Yuting Cui、Zhenxing Zhang、Tatsuya Yamagata、Xuebing Li
DOI:10.1016/j.ejmech.2017.04.006
日期:2017.7
Various neoglycosphingolipids were efficiently synthesized in a one-step reaction by the coupling of free sugars with an N-alkylaminooxy-functionalized ceramide analogue. The bioactivity studies demonstrated that most of these compounds could upregulate the expression of matrix metalloproteinase-9 (MMP-9, extracellular matrix proteins associated with tumor migration) in murine melanoma B16 cells in
Stability studies of hydrazide and hydroxylamine-based glycoconjugates in aqueous solution
作者:Anna V. Gudmundsdottir、Caroline E. Paul、Mark Nitz
DOI:10.1016/j.carres.2008.11.007
日期:2009.2
Glycoconjugates can be readily formed by the condensation of a free-reducing terminus and a strong alpha-effect nucleophile, such as a hydrazide or a hydroxylamine. Further characterization of a series of glycoconjugates formed from xylose, glucose and N-acetylglucosamine, and either p-toluenesulfonyl hydrazide or an N-methylhydroxylamine, was carried out to gain insight into the optimal conditions for the formation of these useful conjugates, and their stability. Their apparent association constants (974 M-1) at pH 4.5; as well, as rate constants for hydrolysis, at pH 4.0, 5.0 and 6.0 (37 degrees C), were determined. The half-lives of the conjugates varied between 3 h and 300 days, All the compounds were increasingly stable as the pH approached neutrality. Conjugate hydrolysis rates mirrored those found for O-glycoside hydrolysis where conjugates formed from electron-rich monosaccharides hydrolyzed more rapidly. (C) 2008 Elsevier Ltd. All rights reserved