Novel Celgene Ligase Inhibitors Regulate Key Cancer Pathways
Additional Preclinical Data to be Presented at 'Targeting Ubiquitinylation for Drug Discovery' Meeting in San Diego, CA on June 24-25, 2002
WARREN, N.J., June 19 /PRNewswire-FirstCall/ -- Celgene Corporation (Nasdaq: CELG - News) researchers presented preclinical data on the Company's extensive portfolio of novel ubiquitin ligases at the Anti-Cancer Drug Discovery and Development Summit in Princeton, NJ. The data presented indicate that novel Celgene ubiquitin ligases alter the stability of key cell-signaling proteins and affect tumorgenesis (the growth of new tumors). Additional data demonstrated that ubiquitin ligases are accessible targets for the development of selective small molecule drugs for the treatment of cancer.
Ubiquitin ligases are important regulatory molecules that maintain normal cellular functions by selectively marking unwanted or damaged proteins for degradation within cells. Ubiquitin-mediated protein modulation regulates a broad range of cellular processes including cell cycle progression, immune response and cell differentiation. When unwanted or abnormal proteins are not properly removed within cells, abnormalities in cellular functions may occur and cause diseases such as cancer and inflammation. For example, many cancers are caused by the inappropriate removal of vital tumor suppressor proteins. There are three classes of ubiquitin ligases (E1, E2 and E3), of which the E3 ubiquitin ligases have the most substrate specificity.
Celgene scientists presented preclinical data on small molecule inhibitors of two proprietary E3 ubiquitin ligases, SMURF (SMAD ubiquitinylation regulatory factor) and the p27 E3 ubiquitin ligase, which regulate key signaling pathways involved in the onset and progression of cancer. The data demonstrate that treatment of cancer cells with inhibitors of the p27 E3 ubiquitin ligase dramatically elevate the level of the p27 tumor suppressor protein, leading to cell cycle arrest and subsequent cell death. Inhibitors of SMURF, which regulates the TGF-beta signaling pathway that plays an essential role in tumorgenesis, have anti-proliferative activity. The data presented indicate that E3 ubiquitin ligases represent a novel class of potential therapeutic targets in cancer.
"The data presented demonstrate that modulation of our proprietary ligases may provide a novel mechanism to regulate tumorgenesis," said Frank Mercurio, Ph.D., Director of Cell-Signaling and Target Discovery of Celgene Corporation. "We have advanced our preclinical program to further evaluate the therapeutic potential of our ubiquitin ligase modulators as anti-cancer agents."
Celgene has established a leading intellectual property estate in the emerging field of ubiquitin ligase-dependent protein degradation that includes thirty-eight proprietary E3 ligases. Celgene scientists have demonstrated that E3 ubiquitin ligases are ideal drug targets because they are amenable to high throughput screening and structural determination. Celgene scientists will present data on the Company's ubiquitin ligase modulators at the "Targeting Ubiquitinylation for Drug Discovery" meeting in San Diego on June 24-25, 2002.
To increase the understanding of ubiquitin ligases and their potential as drug targets, Celgene recently launched ligase.com. The website provides the scientific community with a valuable forum to share information on the role of ubiquitin ligases in the onset and progression of serious diseases.
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Rigl's e-3 candidate is in toxicology studies now and according to company should be IND mid-'03 |
