Bone Resorption Inhibitor

No.162(July 2014)

D4160: Disodium Clodronate Tetrahydrate (1)

Bisphosphonates (BPs) are very effective inhibitors of bone resorption in vivo and in vitro. Disodium clodronate tetrahydrate (1) is one of the BPs and is classified in the first-generation BPs.^1,2)

BPs are known not only as a bone resorption inhibitor but also as an anti-tumor.³⁾ Tumor associated macrophages (TAMs) play many roles in tumor progression; tumor cell growth, migration, invasion, metastasis, and angiogenesis, etc.³⁾ Effects of BPs on TAMs, i.e., BP-induced macrophage depletion, have been reported in detail.³⁾ In such studies, liposome-encapsulated clodronate has been applied for targeting of macrophages.^4-7)

References

1)Bisphosphonates: From bench to bedside
- R. Graham, G. Russell, Ann. N. Y. Acad. Sci. 2006, 1068, 367.
2)Computational insights into binding of bisphosphonates to farnesyl pyrophosphate synthase
- K. Ohno, K. Mori, M. Orita, M. Takeuchi, Curr. Medic. Chem. 2011, 18, 220.
3)Tumour macrophages as potential targets of bisphosphonates
- T. L. Rogers, I. Holen, J. Trans. Med. 2011, 9, 177.
4)Clodronate-liposome-mediated depletion of tumour-associated macrophages: a new and highly effective antiangiogenic therapy approach
- S. M. Zeisberger, B. Odermatt, C. Marty, A. H. M. Zehnder-Fjällman, K. Ballmer-Hofer, R. A. Schwendener, Br. J. Cancer 2006, 95, 272.
5)Targeting tumor-associated macrophages and inhibition of MCP-1 reduce angiogenesis and tumor growth in a human melanoma xenograft
- S. Gazzaniga, A. I. Bravo, A. Guglielmotti, N. van Rooijen, F. Maschi, A. Vecchi, A. Mantovani, J. Mordoh, R. Wainstok, J. Invest. Dermatol. 2007, 127, 2031.
6)Inhibition of bone and muscle metastases of lung cancer cells by a decrease in the number of monocytes/macrophages
- K. Hiraoka, M. Zenmyo, K, Watari, H. Iguchi, A. Fotovati, Y. N. Kimura, F. Hosoi, T. Shoda, K. Nagata, H. Osada, M. Ono, M. Kuwano, Cancer Sci. 2008, 99, 1595.
7)Depletion of tumor-associated macrophages enhances the effect of sorafenib in metastatic liver cancer models by antimetastatic and antiangiogenic effects
- W. Zhang, X.-D. Zhu, H.-C. Sun, Y.-Q. Xiong, P.-Y. Zhuang, H.-X. Xu, L.-Q. Kong, L. Wang, W.-Z. Wu, Z.-Y. Tang, Clin. Cancer Res. 2010, 16, 3420.

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