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/m(2) 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.
journal_name
Expert Opin Investig Drugsjournal_title
Expert opinion on investigational drugsauthors
Kruger EA,Figg WDdoi
10.1517/13543784.9.6.1383subject
Has Abstractpub_date
2000-06-01 00:00:00pages
1383-96issue
6eissn
1354-3784issn
1744-7658journal_volume
9pub_type
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journal_title:Expert opinion on investigational drugs
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更新日期:1998-12-01 00:00:00
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更新日期:2004-11-01 00:00:00
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更新日期:1999-04-01 00:00:00
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