Targeting PTPs with small molecule inhibitors in cancer treatment.
Protein tyrosine phosphorylation plays a major role in cellular signaling. The level of tyrosine phosphorylation is controlled by protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). Disturbance of the normal balance between PTK and PTP activity results in aberrant tyrosine phosphorylation, which has been linked to the etiology of several human diseases, including cancer. A number of PTPs have been implicated in oncogenesis and tumor progression and therefore are potential drug targets for cancer chemotherapy. These include PTP1B, which may augment signaling downstream of HER2/Neu; SHP2, which is the first oncogene in the PTP superfamily and is essential for growth factor-mediated signaling; the Cdc25 phosphatases, which are positive regulators of cell cycle progression; and the phosphatase of regenerating liver (PRL) phosphatases, which promote tumor metastases. As PTPs have emerged as drug targets for cancer, a number of strategies are currently been explored for the identification of various classes of PTP inhibitors. These efforts have resulted many potent, and in some cases selective, inhibitors for PTP1B, SHP2, Cdc25 and PRL phosphatases. Structural information derived from these compounds serves as a solid foundation upon which novel anti-cancer agents targeted to these PTPs can be developed.
Jiang
Zhong-Xing
ZX
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Zhang
Zhong-Yin
ZY
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D016503:Drug Delivery Systems; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors* / Q000187:drug effects
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D017027:Protein Tyrosine Phosphatases