An orally delivered small-molecule formulation with antiangiogenic and anticancer activity

Ofra Benny*, Ofer Fainaru, Avner Adini, Flavia Cassiola, Lauren Bazinet, Irit Adini, Elke Pravda, Yaakov Nahmias, Samir Koirala, Gabriel Corfas, Robert J. D'Amato, Judah Folkman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

161 Scopus citations


Targeting angiogenesis, the formation of blood vessels, is an important modality for cancer therapy. TNP-470, a fumagillin analog, is among the most potent and broad-spectrum angiogenesis inhibitors. However, a major clinical limitation is its poor oral availability and short half-life, necessitating frequent, continuous parenteral administration. We have addressed these issues and report an oral formulation of TNP-470, named Lodamin. TNP-470 was conjugated to monomethoxy-polyethylene glycol-polylactic acid to form nanopolymeric micelles. This conjugate can be absorbed by the intestine and selectively accumulates in tumors. Lodamin significantly inhibits tumor growth, without causing neurological impairment in tumor-bearing mice. Using the oral route of administration, it first reaches the liver, making it especially efficient in preventing the development of liver metastasis in mice. We show that Lodamin is an oral nontoxic antiangiogenic drug that can be chronically administered for cancer therapy or metastasis prevention.

Original languageAmerican English
Pages (from-to)799-807
Number of pages9
JournalNature Biotechnology
Issue number7
StatePublished - Jul 2008
Externally publishedYes

Bibliographical note

Funding Information:
We thank Donald Ingber for his support and encouragement of this work, Daniela Prox and Jenny Mu for their assistance with animal studies and chemical analysis, Kristin Johnson for the graphic work, Chun Wang (University of Minnesota) for fruitful discussions. We thank D. Figg, National Cancer Institute, for TNP-470. This work is supported in part by a Department of Defense Congressional Award W81XWH-05-1-0115 (to J.F.). The submission of this paper was completed before Folkman passed away in January and is dedicated to him for his support and mentorship.


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