Novel Compositions for Cancer Therapy (Proteasomes Inhibitors)
Tech ID: 22376 / UC Case 2011-354-0
BackgroundMedicinal chemistry programs based on natural product leads have generated a large number of synthetic analogues optimized for therapeutic use. The most successful example may be Carfilzomib, inspired in the natural product epoxomicin and currently in phase III clinical trials for multiple myeloma. The promise of proteasome inhibitors is validated by the first-in-class approved drug, Velcade as well as numerous proteasome inhibitors in clinical trials.
Technology DescriptionWithin mammalian cells, proteasome inhibitors block the ability of proteasomes to degrade unneeded or damaged proteins. When administered, proteasome inhibitors have been shown to be effective for treatment of cancer, HIV infection and autoimmune diseases. UC inventors have isolated, characterized and synthesized a natural proteasome inhibitor, discovered from a tropical marine cyanobacteria. Proprietary compositions (parent and analogs), which have intriguing and unique structural features, are claimed for treatment of cancer and other diseases responsive to proteasome inhibition.
ApplicationsWhile most enabled for the treatment of diverse cancers e.g., myeloma, denocarcinoma, pancreatic cancer, B cell-related cancer and lymphomas, proteasomes inhibitors have also demonstrated utility for the treatment of diverse human diseases, including but not limited to retroviral infections such as human immunodeficiency virus-1 (HIV-1) infection, immune disorders, inflammation (epoxomicin), Stroke and neurodegenerative disease (via promotion of neurite outgrowth as described for lactacystin, omurolide, tyropeptin A, curcumin, capsaicin, and TMC-95A).
- Simple synthesis
- Unique structure differentiate claimed compositions from other, known compositions of matter in vitro, in vivo and clinical studies
- Potent activity with low cytotoxicity
- Mechanism of action well understood through
State Of DevelopmentAssay-guided purification was used to identify and isolate the parent compounds, carmaphycins A and B work has demonstrated potent efficacy vs. human lung adenocarcinoma and colon cancer cells. The structures were elucidated by means of NMR and HRESIMS data and absolute and relative configurations were determined by total synthesis. A straightforward synthetic method has generated material sufficient to support in vivo assessment of efficacy of compositions.
Intellectual Property InfoWorldwide rights available; pending patents available under confidentiality.
- Inventor's Bio - 03/19/2012
- Inventor information - 03/19/2012
- Pereira, AR, et al., The Carmaphycins: New Proteasome Inhibitors Exhibiting an a, ß-Epoxyketone Warhead from a Marine Cyanobacterium - 03/01/2012
|Patent Cooperation Treaty||Published Application||WO 2013/010018||01/17/2013||2011-354|
new chemical entity, NCE, composition, therapy, therapeutic, proteasome inhibitor, cancer, HIV, AIDS, autoimmune, inflammation, myeloma, adenocarcinoma, pancreatic cancer, B cell, lymphoma, carmaphysin, caramycin