Novel Oncology Therapeutic: PKB/AKT Inhibitors
Phosphoinositide (PI) signalling is of utmost importance for cellular function and ultimately human health. Phosphoinositides are important regulators of many signal transduction processes. They control such critical processes as cell growth, communication and differentiation, the understanding of which will ultimately lead to treatments for human diseases such as diabetes or cancer. Phosphorylation and phosphate removal performed by various kinases and phosphatases, respectively, as well as the release of the inositol headgroup by phospholipases are the crucial players that control the flux of inositol lipid metabolism. In particular, the influence of PI 3-kinases for cellular signalling is well documented highlighting the importance of this enzyme in oncology and diabetes. Akt/PKB is a central component of the cell survival pathway and thus has been an important target for oncology drugs
| Date added | 24 Apr 2008 |
|---|---|
| Reference number | 23-914 |
| Status | The technology is protected by a patent family at the national stage with a priority date of Feb. 2005. |
| Availability | Further Exemplification – Potential Wellcome Trust Seeding Drug Discovery Award |
| References | [Blank] |
The technology and its advantages
In conjunction with Imperial College we have identified two small molecule inhibitors of the PkB/Akt pathway. One of these hits inhibits PKB by blocking phosphorylation on the two sites that PKB can be activated on, whereas the other appears to inhibit PKB by blocking only one phosphorylation site. Either of these compounds may prove to be promising drug targets. Both are being investigated further and used as points for further rational synthesis.
In parallel work has been carried out to determine the exact molecular mechanism of action of the two compounds. It has been known that some time that the compounds do not inhibit PKB directly. Increasingly the evidence being gathered indicates that the molecular target of our compounds may be MToR.
This programme is currently being funded through proof of concept funding with the aim to get to a patented target::compound pair that would move to either the Q4 or Q1 Seeding Drug Discovery preliminary application, and MRC development award application or funding from the UCLH comprehensive biomedical research centre to get the compound through pre-clinical toxicology to an IND filing. We would then seek to partner.
Market opportunity
The oncology market is forecast to become the second largest within the pharmaceutical industry by 2020, with sales approaching $50 billion annually. This will be driven by the increasing prevalence of cancer and the rising costs of therapy.
A new class of therapies known as molecular targeted therapies (MTTs) has been developed.
It is widely believed that MTTs are the future of cancer therapy and kinase inhibitors are at the forefront of MTTs in development.
Datamonitor anticipate growth in the market for for MTTs from around $7 billion today to around $30 billion by 2015.
Within MTTs in development, signal transduction inhibitors account for 29% of the products being developed.
Further information
Please contact Dr Richard Fagan, UCL Business PLC T 020 7679 9000 E r.fagan@uclb.com
