Protein Tyrosine Kinase Inhibitors
Tyrosine Kinases (TKs) are enzymes that catalyze the addition of a phosphate from ATP to a tyrosine residue on a substrate protein. Tyrosine phosphorylation serves as a molecular signal during embryogenesis and tissue remodeling in adults. TKs can either be trans-membrane proteins linked to a receptor or non-receptor type cytosolic or nuclear. Humans have more than 90 known tyrosine kinases: 58 receptor-linked and 32 cytosolic. The former kinds of TKs are involved in transmembrane signal transduction (growth-factor receptor-mediated signaling) whereas the latter kind is responsible for conveying information to the nucleus of the cell resulting in gene transcriptional regulation. TK function is important in cell division (mitosis) and cell growth. Due to their involvement in cell proliferation, TKs are attractive targets for therapeutic intervention in various forms of cancer. TK inhibitors inhibit proliferation, survival, invasion, and angiogenesis in cancer cells. High TK activity in fibroblasts is directly associated to the ability of these cells to help heal wounds, tissue remodeling and transformation. Deregulation of TKs has been linked to several human developmental abnormalities. Inhibitors help turn off the TKs when they become mutated or get constitutively turned on resulting in aberrant downstream signaling. More than 20 inhibitors ("nibs") have been approved by the U.S. FDA for treatment of various types of cancers. BioVision's portfolio includes a healthy collection of individual TK inhibitors and also convenient sets of inhibitors for specific classes of TKs (for example the receptor-type TK inhibitor set).
