Abstract
Fumagillin, an antimicrobial compound first isolated in 1949 from the fungus Aspergillus fumigatus, four decades later was unexpectedly found to inhibit angiogenesis. Interest in developing angiogenesis inhibitor drugs as possible treatments for cancer led to the synthesis of analogs of fumagillin. Preclinical studies of various analog drugs confirmed that they inhibited angiogenesis, but they also were associated with weight loss as an adverse effect. Because adipose tissue can grow and regress throughout adulthood, is highly vascularized, and has angiogenic properties, interest in investigating anti-angiogenic agents in animal models of obesity found that fumagillin analogs caused dose-dependent reversible weight reduction and adipose tissue loss. Beloranib, a fumagillin analog that is an angiogenesis inhibitor and associated with decreased adiposity in animals, has been studied in phase I clinical trials for cancer. It is currently being investigated for the treatment of obesity and related conditions. Three phase I and three phase II studies found significant degrees of weight loss and acceptable tolerability for beloranib compared to placebo, justifying further clinical development of the drug for obesity.
References
Dec 6, 1990·Nature·D IngberJ Folkman
Nov 18, 1971·The New England Journal of Medicine·J Folkman
Apr 26, 1994·Proceedings of the National Academy of Sciences of the United States of America·R J D'AmatoJ Folkman
Jan 15, 2000·Bioorganic & Medicinal Chemistry Letters·C K HanK T No
Aug 1, 2002·Proceedings of the National Academy of Sciences of the United States of America·Maria A RupnickM Judah Folkman
Jan 18, 1952·Science·J H KILLOUGHR C SMITH
Feb 26, 2004·Nature Medicine·Ronit Satchi-FainaroJudah Folkman
Nov 4, 2004·International Journal of Cancer. Journal International Du Cancer·Eunyoung ChunKi-Young Lee
Feb 3, 2005·Biological & Pharmaceutical Bulletin·Eun-Joo Kim, Won-Ho Shin
Oct 1, 1949·Journal of Bacteriology·F R Hanson, T E Eble
Apr 21, 2007·Journal of Molecular Endocrinology·Yoo Mee KimSung-Kil Lim
Jul 9, 2009·Investigational New Drugs·Sang Joon ShinHyun Cheol Chung
Jan 23, 2010·Obesity·Henri R LijnenBerthe Van Hoef
Feb 2, 2010·Nature Reviews. Drug Discovery·Yihai Cao
Dec 29, 2010·Investigational New Drugs·Sang Joon ShinHyun Cheol Chung
Mar 21, 2013·Obesity·T E HughesJ E Vath
Mar 13, 2014·Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy·Amit A JoharapurkarMukul R Jain
Feb 12, 2015·JAMA Psychiatry·Elizabeth Reisinger WalkerBenjamin G Druss
Citations
Mar 6, 2018·Current Obesity Reports·Gitanjali Srivastava, Caroline Apovian
Nov 17, 2016·Endocrinology·Clinton T Elfers, Christian L Roth
Aug 19, 2015·Nature Chemical Biology·Nancy P Keller