Compounds for Cancer Therapy
- 详细技术说明
- These compounds are potent inhibitors of the isoenzyme PFKFB3,which is over-expressed to enhance glycolysis in most cancer cells. These newlyidentified inhibitors selectively bind to PFKFB3, reduce the Fru-2,6-BP levelsand glycolytic flux, resulting not only in growth inhibition of tumor cells butalso massive cell death. The compoundscan be administered to a patient by any suitable means, including intravenous,parenteral, subcutaneous, intrapulmonary, and intranasal administration.
- *Abstract
-
Basedon the structure of PFKFB3 itself and in complex with its ligands, thecompounds N4A (5,6,7,8-tetrahydroxy-2-(4-hydroxyphenyl)chromene-4-one) and YN1(7,8-dihydroxy-3-(4-hydroxyphenyl)chromen-4-one) were found to be comparativelyselective inhibitors of PFKFB3. Guided by structural basis for inhibitor testing,these inhibitor molecules were optimized using similarity search andcomputational evaluation, resulting in additional compound embodiments with a5-fold improvement in potency. Other compounds and molecules have beenidentified to inhibit PFKFB3 based on the structure and binding of N4A and YN1to PFKFB3 as well as other PFKFB isozymes. The newly identified inhibitors ofPFKFB3 was shown to reduce the Fru-2,6-BP levels and glycolytic flux in HeLacells, resulting not only in growth inhibition but also massive cell death. Thistechnology enables structure-assisted design and development of novel PFKFB3inhibitors as modulators of the glycolytic pathway and as chemotherapeuticagents for cancer.
- *IP Issue Date
- None
- *IP Type
- Utility
- *Licensing
- Robert J. Brown Assistant Director Tel: 225-615-8916 Email: rjbrown@lsu.edu
- 国家
- United States
- 申请号码
- 13/467,764
- 国家/地区
- 美国
