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Novel Proteasome Inhibitors for Treating Cancer
Yeda R&D Co. Ltd Israel flag Israel
Abstract ID:
A unique class of proteasome inhibitors for cancer therapy.Cancer is the second-leading cause of death in the United States after heart disease, and the amount of funding for cancer research — public and private — is higher than for any other disease....
Contact Galit Mazooz, ph.d.
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A unique class of proteasome inhibitors for cancer therapy.


Cancer is the second-leading cause of death in the United States after heart disease, and the amount of funding for cancer research — public and private — is higher than for any other disease. However, despite major advances in the management of cancer, most tumor types are resistant to conventional treatment modalities. Proteasome inhibitors induce selective cell death of malignant cells, and as such represent a promising class of targeted anticancer agents. The current technology involves a unique class of proteasome inhibitors that were discovered using a novel high throughput, image-based screening approach.


Applications






    • Therapeutic agents for the treatment of various malignancies.





    • Proteasome inhibitors are ideal candidates for combination therapy, since they were shown to enhance chemosensitivity and overcome drug resistance.





    • Proteasome inhibitors may serve as research tools to investigate protein degradation in eukaryotic cells.





Advantages


·         The outlined set of proteosome inhibitors target sites other than the 20S catalytic core, thereby offering an alternative mechanism of action, different from the one employed by commercially available inhibitors.


·         Proteasome inhibitors hold the promise of being more selective, thus harming fewer normal cells, reducing side effects, and improving the quality of life.


Technology's Essence


Proteasomal degradation plays an essential role in multiple cellular processes, including cell division and growth, DNA repair and cell cycle control. Despite its widespread distribution and involvement in multiple biological processes in normal cells, the proteasome activity is particularly critical for the survival of transformed cells. Thus, malignant cells are significantly more sensitive to proteasome inhibition than their normal counterparts, and blocking proteasomal degradation may sensitize them to both conventional chemotherapy and radiotherapy. The outlined technology involves a highly sensitive, microscope-aided high throughput screen. It makes use of a fluorescent reporter that translocates into the nucleus upon inhibition of proteasomal activity. Using this screen, several compounds with a pronounced and unique proteasome inhibitory activity were identified.


Licensing Status

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FEATURED
Last Updated May 2016
Technology Type THERAPEUTIC
Phase of Development EARLY STAGE
CORPORATION