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Review

Identification of activators for the M2 isoform of human pyruvate kinase

Douglas Auld  1 , Min Shen  1 , Amanda P Skoumbourdis  1 , Jian-kang Jiang  1 , Matthew Boxer  1 , Noel Southall  1 , James Inglese  1 , Craig Thomas  1
In: Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010.
[updated ].
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Review

Identification of activators for the M2 isoform of human pyruvate kinase

Douglas Auld et al.
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Excerpt

The expression of human pyruvate kinase M2 (hPK-M2) in cancer cells appears to be critical for tumor cell growth and proliferation in vivo. Because the PK-M2 isoform is expressed in all cancer cells studied, it represents a target for drug development that could potentially enable tumor cells to return to a normal state of metabolism. If this novel strategy for targeting malignancy were successful, it would be applicable to diverse types of cancer. The probes ML083 (CID-650361) and ML082 (CID-654376) are members of a series of highly specific allosteric activators for the tumor-specific isoform of human pyruvate kinase (M2 isoform). Both probes affect the cooperativity of phosphoenolpyruvate (PEP) binding with little effect on adenosine diphosphate (ADP) binding in a manner similar to FBP.

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