Current Medicinal Chemistry - Volume 12, Issue 1, 2005

Protein tyrosine phosphatase (PTP) is the family of enzymes that are key players in cellular signal transduction system and perturbation in their functioning is implicated in many disease-states. Diverse chemical compounds are being synthesized and evaluated as PTP inhibitors. This review presents a brief account of various enzymes of the PTP family and their inhibitors. Peculiar features of these enzymes and their roles in various diseases are summarized along with important inhibitors developed in recent years.

This review aim to demonstrate the role of bioisosterism in rational drug design as well as in the molecular modification and optimization process aiming to improve pharmacodynamic and pharmacokinetic properties of lead compounds.

The αvβ3 receptor, which are members of the group of the cellular adhesion molecules (CAM), are heterodimeric transmembrane glycoprotein receptors involved in processes such as cell-cell and cell-matrix adhesion, cell migration and signaling. Integrin αvβ3 receptor is expressed on almost all cells originating from the mesenchyme and seem to mediate several biological processes, including adhesion of osteoblasts to the bone matrix, migration of vascular smooth muscle cells, and angiogenesis. Many efforts were done in the last 10 years to individuate inhibitors for αvβ3 receptors, due to their involvement in important pathophysiological functions. In fact, selective αvβ3 antagonists offer new therapeutic opportunities for the treatment of several human pathologies like osteoporosis, restenosis and diseases involving neovascularization such as rheumatoid arthritis, tumor induced angiogenesis and metastasis. Purpose of this account is to summarize the recent developments in the field of non-peptidic αvβ3 antagonists.

In this account we summarise recent studies on oligonucleotides and oligonucleotide derivatives and their utilisation in antigene, antisense and decoy approaches, with particular attention to peptide nucleic acids, locked nucleic acids and oligonucleotide conjugates, the most promising compounds in this field.