- Title
- Cantharimides: a new class of modified cantharidin analogues inhibiting protein phosphatases 1 and 2A
- Creator
- McCluskey, Adam; Walkom, Cecilia; Bowyer, Michael C.; Ackland, Stephen P.; Gardiner, Emma; Sakoff, Jennette A.
- Relation
- Bioorganic & Medicinal Chemistry Letters Vol. 11, Issue 22, p. 2941-2946
- Publisher Link
- http://dx.doi.org/10.1016/S0960-894X(01)00594-7
- Publisher
- Elsevier Science
- Resource Type
- journal article
- Date
- 2001
- Description
- Cantharidin and its analogues have been of considerable interest as potent inhibitors of the serine/threonine protein phosphatases 1 and 2A (PP1 and PP2A). However, limited modifications to the parent compounds is tolerated. As part of an on-going study we have developed a new series of cantharidin analogues, the cantharimides. Inhibition studies indicate that cantharimides possessing a D- or L-histidine, are more potent inhibitors of PP1 and PP2A (PP1 IC₅₀=3.22±0.7 μM; PP2A IC₅₀=0.81±0.1 μM and PP1 IC₅₀=2.82±0.6 μM; PP2A IC₅₀=1.35±0.3 μM, respectively) than norcantharidin (PP1 IC₅₀=5.31±0.76 μM; PP2A IC₅₀=2.9±1.04 μM) and essentially equipotent with cantharidin (PP1 IC₅₀=3.6±0.42 μM; PP2A IC₅₀=0.36±0.08 μM). Cantharimides with non-polar or acidic amino acid residues are only poor inhibitors of PP1 and PP2A.
- Subject
- cantharidin; cantharidin analogues; cantharimides
- Identifier
- http://hdl.handle.net/1959.13/26962
- Identifier
- uon:1259
- Identifier
- ISSN:0960-894X
- Language
- eng
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