Structure-based approach to nanomolar, water soluble matrix metalloproteinases inhibitors (MMPIs).

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Citation

Attolino E, Calderone V, Dragoni E, Fragai M, Richichi B, Luchinat C, Nativi C

Structure-based approach to nanomolar, water soluble matrix metalloproteinases inhibitors (MMPIs).

Eur J Med Chem. 2010 Dec;45(12):5919-25. doi: 10.1016/j.ejmech.2010.09.057. Epub 2010 Oct 20.

PubMed ID
20965620 [ View in PubMed
]
Abstract

N-arylsulfonyl-based MMPs inhibitors (MMPIs) are among the most prominent inhibitors possessing nanomolar affinity. However, their poor bioavailability remains critical for the drug development of this family of molecules. The structural analysis of the complex of NNGH (the most representative member of the family) with MMP-12 provided us with the basis to effectively design simple NNGH analogues with enhanced solubility in water. Following this approach, the sec-butyl residue, not directly involved in the binding with MMP, has been replaced with hydrophilic residues thus yielding new potent inhibitors soluble in water.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
N-ISOBUTYL-N-[4-METHOXYPHENYLSULFONYL]GLYCYL HYDROXAMIC ACIDMacrophage metalloelastaseKi (nM)4.3N/AN/ADetails