Advantages
- Highly effective in inhibiting MetAP2 when administered orally (proven in animal experiments)
- Wide range of expandability in derivative structure development of compounds
Background and Technology
The microbial metabolite fumagillin, a compound similar to ovalicin, has an inhibitory effect on MetAP2, an important enzyme involved in protein synthesis. MetAP2 inhibitors have anti-Entamoeba histolytica activity and anti-cancer and anti-obesity effects by inhibiting angiogenesis. To date, several pharmaceutical companies have synthesized and developed fumagillin derivatives, but clinical trials were halted during phase 2 or 3 due to concerns about side effects.
Ovalicin is known as a component of an entomopathogenic fungus, and although it has a partially different skeletal structure from fumagillin, it has the same MetAP2 inhibitory effect. We were the first in the world to identify the biosynthetic pathway of ovalicin and developed a method to biosynthesize large amounts of ovalicin precursor compounds using a biosynthetic engineering approach. Ovalicin precursor compounds exhibited anti-Entamoeba histolytica activity (in vitro) that was 5-6 times higher than the native form of ovalisin. Furthermore, we artificially synthesized derivatives from the ovalicin precursors, improved their pharmacokinetics, and developed new compounds that showed high anti-Entamoeba histolytica activity in animal experiments (oral administration) (Figure). These ovalicin precursors and derivatives have the potential to become drug seed/lead compounds for anti-Entamoeba histolytica drugs, anti-cancer drugs, and anti-obesity drugs that have improved the problematic side effects of fumagillin derivatives.
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Reference and Patent
- Presented at academic conference.
- Patent pending (unpublished)
Principal Investigator
Tuta TSUNEMATSU (Nagoya University Graduate School of Bioagricultural Sciences)
Current Stage and Next Step
- Laboratory-synthesized compounds have demonstrated MetAP2 inhibitory activity and anti-Entamoeba histolytica activity in vitro and in vivo. We are planning demonstration research on anti-cancer and anti-obesity effects.
- We seek partnerships with companies interested in seed/lead compounds for therapeutic drugs for diseases such as Entamoeba histolytica, cancer, and obesity.
- Compounds can be provided from the laboratory. Evaluation and feasibility studies are possible using CDA/MTA.
Project No.BK-04460