Anti-cancer agents in medicinal chemistry
-
Anticancer Agents Med Chem · Feb 2009
ReviewRole of tyrosine phosphatase inhibitors in cancer treatment with emphasis on SH2 domain-containing tyrosine phosphatases (SHPs).
Protein tyrosine phosphorylation is one of the key mechanisms involved in signal transduction pathways. This modification is regulated by concerted action of protein tyrosine phosphatases and protein tyrosine kinases. Deregulation of either of these key regulators lead to abnormal cellular signaling, which is largely associated with human pathologies including cancer. ⋯ In this review we describe the progressive efforts and challenges concerning the development of drugs targeting phosphatases as promising novel cancer therapies. We focus on two key regulatory SH2 domain-containing phosphatases, SHP-1 and SHP-2 and one of their substrates, signal regulatory protein alpha. Since SHPs have been linked to many different malignancies, protein tyrosine phosphatases could offer a great spectrum of new, targeted drugs.