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Comment
. 2014 Apr 15;20(8):2026-8.
doi: 10.1158/1078-0432.CCR-14-0166. Epub 2014 Mar 14.

SETting OP449 into the PP2A-activating drug family

Paolo Neviani  1 , Danilo Perrotti
Affiliations
Comment

SETting OP449 into the PP2A-activating drug family

Paolo Neviani et al. Clin Cancer Res. .

Abstract

The protein phosphatase 2A (PP2A) tumor suppressor is inactivated in different leukemias through the activity of its endogenous inhibitors (e.g., SET), which are aberrantly regulated by oncogenic tyrosine kinases. Like other effective and nontoxic PP2A-activating drugs (PAD), OP449 inhibits SET and impairs leukemogenesis. This further supports the immediate use of PADs in patients with leukemia.

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Figures

Figure 1
Figure 1. PP2A and SET-binding PADs in leukemias
Regulation of the PP2A tumor suppressor in leukemias (i.e. CML, AML, MPN, Ph+ ALL) and possible use of PP2A Activating Drugs (PADs; e.g. OP449, FTY720, OSU-2S) in combination with tyrosine kinase inhibitors (TKIs) or conventional chemotherapy for treating leukemias characterized by SET-dependent inactivation of PP2A. OP449 and other PADs exert their anti-leukemic activity upon interaction with SET and inhibition of its ability to interact with PP2A catalytic subunit (PP2Ac) and inhibit PP2A phosphatase activity.
See this image and copyright information in PMC

Comment on

References

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