INNO-206, the (6-maleimidocaproyl hydrazone derivative of doxorubicin), shows superior antitumor efficacy compared to doxorubicin in different tumor xenograft models and in an orthotopic pancreas carcinoma model

被引：64

作者：

Graeser, R. ^{[1
,2
]}

Esser, N. ^{[1
,2
]}

Unger, H. ^{[1
]}

Fichtner, I. ^{[3
]}

Zhu, A. ^{[4
]}

Unger, C. ^{[1
]}

Kratz, F. ^{[1
]}

机构：

[1] Tumor Biol Ctr, Dept Med Oncol, D-79106 Freiburg, Germany

[2] ProQinase GmbH, D-79106 Freiburg, Germany

[3] Max Delbruck Ctr Mol Med, D-13122 Berlin, Germany

[4] Innov Pharmaceut, New York, NY 10022 USA

来源：

INVESTIGATIONAL NEW DRUGS | 2010年 / 28卷 / 01期

关键词：

Doxorubicin; (6-Maleimidocaproyl)hydrazone derivative of doxorubicin; INNO-206; Prodrug; Human serum albumin; Tumor models; ALBUMIN-BINDING PRODRUG; ENDOGENOUS SERUM-ALBUMIN; DOXO-EMCH; CANCER-CHEMOTHERAPY; DRUG CARRIER;

D O I：

10.1007/s10637-008-9208-2

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The (6-maleimidocaproyl)hydrazone derivative of doxorubicin (INNO-206) is an albumin-binding prodrug of doxorubicin with acid-sensitive properties that is being assessed clinically. The prodrug binds rapidly to circulating serum albumin and releases doxorubicin selectively at the tumor site. This novel mechanism may provide enhanced antitumor activity of doxorubicin while improving the overall toxicity profile. Preclinically, INNO-206 has shown superior activity over doxorubicin in a murine renal cell carcinoma model and in breast carcinoma xenograft models. In this work, we compared the antitumor activity of INNO-206 and doxorubicin at their respective maximum tolerated doses in three additional xenograft models (breast carcinoma 3366, ovarian carcinoma A2780, and small cell lung cancer H209) as well as in an orthotopic pancreas carcinoma model (AsPC-1). INNO-206 showed more potent antitumor efficacy than free doxorubicin in all tumor models and is thus a promising clinical candidate for treating a broad range of solid tumors.

引用

页码：14 / 19

页数：6

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