Out-licensing

Development of Wortmannin Conjugates: Targeted-Delivery for the Treatment of Cancer, Arthritis and other Inflammatory Diseases

Introduction/Background

Overactivity of the signal transduction molecule phosphoinositide 3-OH kinase (PI3K) has a significant role in the progression of cancer and inflammatory disease. In fact, PI3K mutations have been increasingly identified in 50% of solid tumours and 30% of breast cancers. With this link to cancer, PI3K is rapidly becoming a central target for anti-cancer therapy. Wortmannin, a specific PI3K inhibitor has potent anti-proliferative and anti-inflammatory activities but has been unsuitable for clinical applications due to its inherent toxicity and instability in cells.

Aims/Hypothesis

We aim to develop Wortmannin conjugates that achieve slow- or controlled-release forms of Wortmannin with improved bioavailability, better stability and reduced toxicity.

Research

To overcome these limitations, the world-renowned expert in PI3K, Dr. Lew Cantley and leading radiologist Dr. Lee Josephson have identified and synthesized novel PI3K inhibitors suitable for cancer treatment. These leading scientists have developed Wortmannin conjugates for both drug delivery and classical medicinal chemistry. The Wortmannin conjugates or pro-drugs can be delivered as targeted or slow release forms of Wortmannin that may inhibit PI3K in tissues more selectively than the parent Wortmannin. These pro-drugs conjugated to specific antibodies and peptides achieve targeted delivery of Wortmannin resulting in localized concentrations of the drug and reducing systemic toxicity. This targeted approach affords the additional advantage of delivering both Wortmannin and other anti-proliferative or anti-inflammatory molecules to effect inhibition of PI3K and other molecular pathways. The development of PI3K inhibitors is essential for the treatment of diseases in which inhibiting cellular proliferation or inflammation is beneficial.

Conclusion

PI3K inhibitors are potential therapeutic drugs for treating cancer and inflammatory diseases. Wortmannin conjugates may be delivered locally or systemically making it a treatment for a broad spectrum of acute and chronic indications. Some diseases that would benefit from PI3K inhibition are breast and prostate cancer, anaphylactic reactions, spinal chord trauma, shock, allergic reactions and arthritis.

Relevance/Opportunity

Research to synthesize and characterize the efficacy of Wortmannin conjugates is ongoing. A partnership opportunity is available for the discovery and subsequent development of novel therapeutics for cancer treatment. Technology licensing opportunity is also available. Please enquire quoting reference no. 952.

Preclinical

Provisional Application submitted September 1, 2005