Doxorubicin immunoconjugates containing bivalent, lysosomally-cleavable dipeptide linkages

被引：31

作者：

Dubowchik, GM

Radia, S

Mastalerz, H

Walker, MA

Firestone, RA

King, HD

Hofstead, SJ

Willner, D

Lasch, SJ

Trail, PA

机构：

[1] Bristol Myers Squibb Pharmaceut Res Inst, Wallingford, CT 06492 USA

[2] Bristol Myers Squibb Pharmaceut Res Inst, Princeton, NJ 08543 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2002年 / 12卷 / 11期

关键词：

D O I：

10.1016/S0960-894X(02)00194-4

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Bivalent doxorubicin (DOX)-dipeptides (16a-c) were prepared and conjugated to the monoclonal antibody BR96. The dipeptides are cleaved by lysosomal proteases following internalization of the resulting immunoconjugates. Conjugate 18b demonstrated antigen-specific in vitro tumor cell killing activity (IC50 = 0.2 muM) that was equipotent to DOX with a near doubling of drug molecules/MAb. Size exclusion chromatography showed 18b to be a noncovalent dimer that was formed immediately upon conjugation. (C) 2002 Elsevier Science Ltd. All rights reserved.

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页码：1529 / 1532

页数：4

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