In order to engineer efficient drugs, it is very important to know the precise mode of action of the active compound. It is therefore of crucial importance to find out what signal transduction pathway(s) it interferes with, and furthermore to localise its target molecules. This is most wanted information as it will lead to improvement of the specificity of the drug and the elimination of unwanted side effects.
The overall aim of the proposed research is the development of specific anti-proliferating drugs which can be easily administered for therapeutic use as anti-cancer agents. As lead compound will be taken: the somatostatin analog TT-232 does not exhibit endocrine effects, it does not inhibit the release of growth hormone, and is not toxic at doses as high as 120 mg/kg body weight. The peptide has been shown to interfere with intracellular tyrosine phosphorylation events, so that is clearly involved in the attenuation of growth factor signalling pathways. A major practical problem in the development of a useful peptide-compound is not only the selectivity of the anti-cancer drug for cancer cells, but also the efficient delivery of the active peptide to the tumor: peptides are often poorly absorbed and easily degraded, so that oral administration for instance is very difficult. Therefore, TT-232 will be tailored for oral administration by its conjugation to lipoamino acids, and its mode of action will be investigated by a detailed study of its interference with known growth factor dependent mitogenic signalling pathways. The intracellular target of TT-232 related products and their lipoamino acid conjugates. Analogous more potent compounds with similar function will be developed and customised for specific purposes.
Funding SchemeCSC - Cost-sharing contracts
1444 Budapest Viii
WC1N 1AX London