AxCell Biosciences, a subsidiary of Cytogen Corporation, has signed a Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute (NCI) for the application of AxCell's proprietary protein interaction mapping technology in order to research two major signal transduction families, tyrosine kinases and serine-threonine kinases, and how they impact signaling pathways within cells. Ultimately, this research could lead to the development of new drugs to treat cancer and other diseases.

According to the CRADA, the parties will collaborate to study two major signal transduction families, tyrosine kinases and serine-threonine kinases, and how they impact signaling pathways within cells. To accomplish this, the research aims to predict and validate sites of phosphorylation of human proteins, the effects of that phosphorylation on binding interactions of such proteins, and to identify "recruitment sites" which facilitate peptide phosphorylation by binding to kinase domains at regions distinct from the catalytic cleft.

Research under this CRADA will focus on two subfamilies of these kinases that are known to be particularly important in cancer biology: the PKC family of serine threonine kinases and the src family of tyrosine kinases.

Under the terms of the CRADA, AxCell will have an exclusive option to elect a commercialization license to all inventions arising from the CRADA research, such as novel drug candidates and new methods of screening such candidates. The CRADA will allow AxCell to commercialize the new inventions by moving the resulting products forward to the marketplace. In addition, novel data and information derived from the CRADA that is relevant to AxCell's ProChart dataset of signal transduction pathway content will be added to ProChart subject to certain terms and conditions.

AxCell's systems biology approach to drug discovery involves the efficient identification of peptide ligands that bind to modular domains on signaling proteins. These peptides are used to identify additional signaling proteins, which share that domain. Bioinformatic analysis of the ligands and signaling proteins leads to identification of additional peptides and proteins and the pathways in which they are active. This may lead to identification of targets that can be validated in biological models and formatted in high throughput assays to screen against natural product and small molecule libraries for potential inhibitors or modulators of these validated targets.

Using this approach, AxCell is building one of the most complete and systematic maps of protein interactions involved in human cell signaling. This data set - known commercially as the ProChart database - includes the first and only complete map of the known WW protein domains, which are believed to have an impact on health problems including hypertension, muscular dystrophy and immunodeficiency.

AxCell is continuing to chart increasingly greater portions of the proteome, such as the SH3 and PDZ domain families, and is adding new results to ProChart on a regular basis. AxCell is actively utilizing ProChart to further elucidate the role of novel proteins and pathways, through both external collaborations and internal data mining.