Inhibitors of autophosphorylation protein kinases

Abstract

The subject invention concerns peptide molecules that specifically inhibit the enzymatic function of tyrosine kinases, including the JAK and EGF receptor (EGFR) family of kinases, to autophosphorylate, i.e., to transfer a phosphate group from ATP to an amino acid in the kinase. Phosphorylation of proteins is the most fundamental method for signal transduction among proteins in a cell. Inhibition of tyrosine kinase autophosphorylation activities inhibits the enzyme's signaling and shuts down the functioning pathways originating from the enzyme. The JAK2 and EGFR tyrosine kinases are involved in both inflammatory disorders and cancer. In these disorders, the tyrosine kinases can often be activated in an uncontrolled fashion. The subject application also concerns antibodies that bind to a tyrosine kinase autophosphorylation site. The subject invention also concerns pharmaceutically acceptable formulations of the subject peptides and antibodies, and methods for treating inflammatory and oncological disorders by inhibiting tyrosine kinase signaling in these situations by administering a peptide or antibody of the present invention.