Synthesis of Gem-Bisphosphonic Doxorubicin Conjugates

Fabulet, O.; Sturtz, G.

doi:10.1080/10426509508042521

Cited by 17 publications

(10 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, several groups previously synthesized and tested various bisphosphonate-anti-neoplastic drug conjugates with the cytotoxic agents, methotrexate, melphalan, doxorubicin, or cis-platinum covalently attached via an amide bond using the terminal amino group of pamidronate [37–40]. The in vivo activity of these compounds was modest and no data were presented on stability or accumulation kinetics in bone.…”

Section: Discussionmentioning

confidence: 99%

A promising approach for treatment of tumor-induced bone diseases: Utilizing bisphosphonate derivatives of nucleoside antimetabolites

Reinholz

Zinnen

Dueck

et al. 2010

Bone

View full text Add to dashboard Cite

Despite palliative treatments, tumor-induced bone disease (TIBD) remains highly debilitating for many cancer patients and progression typically results in death within two years. Therefore, more effective therapies with enhanced antiresorptive and cytotoxic characteristics are needed. We developed bisphosphonate-chemotherapeutic conjugates designed to bind bone and hydrolyze, Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Conflicts of Interest:Dr. Monica Reinholz received research funding for supplies and animals from MBC Pharma to supplement a portion of the in vivo efficacy studies that was not supported by the NIH grants. Dr. Reinholz, her spouse, or any of her dependents have no personal financial interest (such as company stocks or shares or equity) in MBC Pharma. Drs. Zinnen, Sebesta, and Karpeisky were employees of MBC Pharma at the time the work was performed. All other co-authors have no personal financial interest in MBC Pharma or conflicts of interest. NIH Public Access Author ManuscriptBone. Author manuscript; available in PMC 2011 July 1. Published in final edited form as:Bone. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript releasing both compounds, thereby targeting both osteoclasts and tumor cells. This study examined the effects of our lead compound, MBC-11 (the anhydride formed between arabinocytidine (AraC)-5'-phosphate and etidronate), on bone tumor burden, bone volume, femur bone mineral density (BMD), and overall survival using two distinct mouse models of TIBD, the 4T1/luc breast cancer and the KAS-6/1-MIP1α multiple myeloma models. In mice orthotopically inoculated with 4T1/luc mouse mammary cells, MBC-11 (0.04 µg/day; s.c.) reduced the incidence of bone metastases to 40% (4/10), compared to 90% (9/10; p=0.057) and 100% (5/5; p=0.04) of PBS-or similarly-dosed, zoledronate-treated mice, respectively. MBC-11 also significantly decreased bone tumor burden compared to PBS-or zoledronate-treated mice (p=0.021, p=0.017, respectively). MBC-11 and zoledronate (0.04 µg/day) significantly increased bone volume by two-and four-fold, respectively, compared to PBS-treated mice (p=0.005, p<0.001, respectively). In mice systemically injected with human multiple myeloma KAS-6/1-MIP1α cells, 0.04 and 4.0 µg/day MBC-11 improved femur BMD by 13% and 16%, respectively, compared to PBS (p=0.025, p=0.017, respectively) at 10 weeks post-tumor cell injection and increased mean survival to 95 days compared to 77 days in mice treated with PBS (p=0.047). Similar doses of zoledronate also improved femur BMD (p≤0.01 vs PBS) and increased mea...

show abstract

Section: Discussionmentioning

confidence: 99%

A promising approach for treatment of tumor-induced bone diseases: Utilizing bisphosphonate derivatives of nucleoside antimetabolites

Reinholz

Zinnen

Dueck

et al. 2010

Bone

View full text Add to dashboard Cite

show abstract

“…Keppler et al found that therapeutic efficacy of a bisphosphonatecisplatin analogue was not superior to conventional cisplatin in a transplantable osteosarcoma model, even at a 28-fold higher dose [10]. No antitumor effect at all was obtained when amino group of doxorubicin was used to incorporate bisphosphonate when evaluated against human tumor xenografts [11].…”

Section: Introductionmentioning

confidence: 98%

RGD peptide conjugated liposomal drug delivery system for enhance therapeutic efficacy in treating bone metastasis from prostate cancer

Wang

Chen

Zhang

et al. 2014

Journal of Controlled Release

164

112

View full text Add to dashboard Cite

“…The chemical linkage of the compounds is the determining factor for stability, pharmacokinetic and pharmacological properties of such bonetargeting conjugates. Several previously synthesized BPconjugates linking antitumor agents to BPs only showed modest anticancer activities [10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

In vitro and in vivo toxicity of 5-FdU-alendronate, a novel cytotoxic bone-seeking duplex drug against bone metastasis

et al. 2015

View full text Add to dashboard Cite

show abstract

Synthesis of Gem-Bisphosphonic Doxorubicin Conjugates

Cited by 17 publications

References 10 publications

A promising approach for treatment of tumor-induced bone diseases: Utilizing bisphosphonate derivatives of nucleoside antimetabolites

A promising approach for treatment of tumor-induced bone diseases: Utilizing bisphosphonate derivatives of nucleoside antimetabolites

RGD peptide conjugated liposomal drug delivery system for enhance therapeutic efficacy in treating bone metastasis from prostate cancer

In vitro and in vivo toxicity of 5-FdU-alendronate, a novel cytotoxic bone-seeking duplex drug against bone metastasis

Contact Info

Product

Resources

About