Description of Invention:
Signal transduction processes underlie the transfer of extracellular information to the interior of the cell and ultimately to the nucleus. A variety of signal transduction processes are critical for normal cellular homeostasis, with protein-tyrosine kinases (PTKs) playing central roles in many of these pathways. Examples of such PTKs include the PDGF receptor, the FGF receptor, the HGF receptor, members of the EGF receptor family, such as the EGF receptor, erb-B2, erb-B3 and erb-B4, the src kinase family, Fak kinase and the Jak kinase family. Protein-tyrosine phosphorylation that results from the action of PTKs can modulate the activity of certain target enzymes as well as facilitate the formation of specific multi-protein signaling complexes through the actions of homologous protein modules termed Src homology 2 (SH2) domains, which recognize specific phosphotyrosyl containing sequences. A malfunction in this system through tyrosine kinase overexpression and/or deregulation can be manifested by various oncogenic and hyperproliferative disorders, including cancers, inflammation, autoimmune disease, hyperproliferative skin disorders, psoriasis and allergy/asthma, etc. The disclosed compounds, e.g. peptides, preferably, macrocyclic peptides, are Grb2 SH2 domain signaling antagonists with enhanced binding affinity. The claims of the current application are directed to compositions of matter and methods of use which provide for the diagnosis, testing and treatment of the aforementioned disease states.
Applications:
For treatment of cancer, inflammation, autoimmune diseases, hyperproliferative skin disorders, psoriasis and asthma.
Development Status:
The technology is currently in an early pre-clinical stage of development.
