Targeting PTPs with small molecule inhibitors in cancer treatment |
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Authors: | Zhong-Xing Jiang Zhong-Yin Zhang |
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Institution: | (1) Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, IN 46202, USA |
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Abstract: | 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. |
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Keywords: | Protein tyrosine phosphatase (PTP) PTP1B SHP2 Cdc25 PRL phosphatases Small molecule inhibitor design PTP inhibitor |
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