Gemcitabine–Ibandronate Conjugate Enables the Bone-Targeted Combination Therapy in Bone Cancer: Synthesis and Efficacy in Combination with Docetaxel
| Autor: | Shawn Zinnen, Alexander Karpeisky, Kristen B. Farrell, Douglas H. Thamm |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Pharmacology
endocrine system diseases Combination therapy Bone disease Chemistry Bone cancer medicine.medical_treatment Organic Chemistry Biomedical Engineering Pharmaceutical Science Bioengineering Docetaxel Bisphosphonate medicine.disease Article Gemcitabine Cancer research medicine Osteosarcoma Biotechnology Conjugate medicine.drug |
| Zdroj: | Bioconjug Chem |
| ISSN: | 1520-4812 1043-1802 |
| DOI: | 10.1021/acs.bioconjchem.1c00507 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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