Gemcitabine-Ibandronate Conjugate Enables the Bone-Targeted Combination Therapy in Bone Cancer: Synthesis and Efficacy in Combination with Docetaxel

被引：4

作者：

Farrell, Kristen B. ^{[1
]}

Zinnen, Shawn ^{[1
]}

Thamm, Douglas H. ^{[2
]}

Karpeisky, Alexander ^{[1
]}

机构：

[1] MBC Pharma Inc, Aurora, CO 80045 USA

[2] Colorado State Univ, Flint Anim Canc Ctr, Ft Collins, CO 80523 USA

来源：

BIOCONJUGATE CHEMISTRY | 2021年 / 32卷 / 12期

关键词：

TRIFLUOROACETIC-ANHYDRIDE; TUMOR; BISPHOSPHONATES; EPIDEMIOLOGY;

D O I：

10.1021/acs.bioconjchem.1c00507

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

Patients with cancer-induced bone disease, including primary bone cancers such as osteosarcoma (OS) and metastases from other tissues of origin, present a high unmet medical need. We present a potential therapeutic approach built upon a proven bone-targeting bisphosphonate conjugate platform with the known synergies of gemcitabine (GEM) and docetaxel (DTX). The synthesis of rationally designed GEM- IB, the conjugate of GEM-5 '-phosphate with ibandronate (IB), is presented. GEM-IB as a single agent or in combination with DTX demonstrated reduced tumor burden, preservation of the bone architecture, and improved the survival in a murine model of OS. This is the first demonstration of a bone-targeting conjugate in combination with a second drug to create effective drug ratios in the bone compartment.

引用

页码：2530 / 2539

页数：10

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