Since the discovery of fumagillin and its molecular target MetAP2, many papers have been published by researchers from all over the world. Below are a few, key references to MetAP2, fumagillin and the backbone polymer HPMA.
Methionine aminopeptidase 2 (MetAP2) is an important enzyme in the regulation of a number of cellular processes including protein turnover, protein targeting and cell proliferation.
- Bernier et al. Journal of Cellular Biochemistry 2005, 95 1191–1203 “Methionine Aminopeptidases Type I and Type II Are Essential to Control Cell Proliferation”
Fumagillol is the active part of the natural product fumagillin. Many small molecule fumagillol derivatives, including TNP-470 (Takeda), PPI-2458 (Praecis) and CKD-732 (Chong Kun Dang), have been studied pre-clinically and clinically.
- Hannig et al. Drugs of the Future 2005, 30, 497-508 “Fumagillin class inhibitors of methionine aminopeptidase-2”
The clinical utility of fumagillol derivatives is discussed by Hughes (obesity – beloranib/CKD-732) and Herbst (non-small cell lung cancer – TNP-470).
- Hughes Obesity 2013 21, 1782-8 “Ascending Dose Controlled Trial of Beloranib, a Novel Obesity Treatment for Safety, Tolerability and Weight Loss in Obese Women”
- Herbst et al. J. Clin Onc. 2002 20, 4440-4447 “Safety and Pharmacokinetic Effects of TNP-470, an Angiogenesis Inhibitor, Combined With Paclitaxel in Patients With Solid Tumors: Evidence for Activity in Non–Small-Cell Lung Cancer”
The bio-medical uses of HPMA and its copolymer conjugates have been extensively investigated pre-clinically and clinically since their original synthesis in the 1970’s.
- Kopecek et al. Adv. Drug Delivery Reviews 2010, 62, 122–149 “HPMA copolymers: Origins, early developments, present, and future”