TNP-470: An angiogenesis inhibitor in clinical development for cancer

E. A. Kruger, W. D. Figg*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

128 Scopus citations

Abstract

TNP-470, an analogue of fumagillin, has been shown to inhibit angiogenesis in vitro and in vivo. In 1992, TNP-470 entered clinical development for cancer as an anti-angiogenic agent. It is currently in Phase I/II trials in Kaposi's sarcoma, renal cell carcinoma, brain cancer, breast cancer, cervical cancer and prostate cancer. In early clinical reports, TNP-470 is tolerated up to 177 mg/m2 with neurotoxic effects (fatigue, vertigo, ataxia, and loss of concentration) being the principal dose limiting toxicity (DLT). Terminal half-life values are short and have shown intermittent and intrapatient variation (range: 0.05-1.07 h). Recently, mechanistic studies have identified cell cycle mediators and the protein methionine aminopeptidase-2 (MetAP-2) as molecular targets of TNP-470 and fumagillin. Animal studies confirm some toxic effects on normal angiogenic processes such as the female reproductive system and wound healing, which will require caution and close monitoring in the clinic. TNP-470 is one of the first anti-angiogenic compounds to enter clinical trials, making it a valuable prototype for future trials of angiogenesis inhibitors in oncology.

Original languageEnglish
Pages (from-to)1383-1396
Number of pages14
JournalExpert Opinion on Investigational Drugs
Volume9
Issue number6
DOIs
StatePublished - 2000
Externally publishedYes

Keywords

  • AGM-1470
  • Angiogenesis
  • Cancer
  • Fumagillin
  • Neovascularisation
  • Therapy
  • Tumours

Fingerprint

Dive into the research topics of 'TNP-470: An angiogenesis inhibitor in clinical development for cancer'. Together they form a unique fingerprint.

Cite this