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values lower than 30 µM. aa Most notable were library members 314{2,1,27} and 314{2,1,19}
(Figure 5.4) with IC50 values of 8.0 µM and 8.3 µM, respectively. Both pyrroles showed high
selectivity for MKP-1 over other phosphatases, including the dual-specificity phosphatase MKP-
3. Importantly, the pyrroles 314{2,1,27} and 314{2,1,19} were identified as the most potent
inhibitors of MKP-1 from a broader screen of over 65,000 compounds from the NIH repository
(http://pubchem.ncbi.nlm.nih.gov/assay/assay.cgi?aid=374). These promising results have
prompted further studies into the mechanism of action of 314{2,1,27} and 314{2,1,19} and
development of more potent analogues.
aa Biological tests were performed by Mr. John J. Skoko under the supervision of Professor John S. Lazo.
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