The inhibition of protein phosphatases 1 and 2A: a new target for rational anti-cancer drug design?
McCluskey, A.; Ackland, S.P.; Gardiner, E.; Walkom, C.C.; Sakoff, J.A.
Anti-Cancer Drug Design 16(6): 291-303
2001
ISSN/ISBN: 0266-9536 PMID: 12375882 Document Number: 535746
Recent investigations in our laboratories have highlighted that the inhibition of the serine/threonine protein phosphatases 1 and 2A (PP1 and PP2A) is an excellent target for the development of novel anti-cancer agents. Using a combination of the known crystal structure of PP1 and the modelled structure of PP2A, we have rationally designed a new class of protein phosphatase inhibitors, cantharimides, which exhibit broad-spectrum anti-cancer activity. Synthetic modifications of the simplest known PP1 and PP2A inhibitor, norcantharidin, has led to the development of potent PP1 and PP2A inhibitors.