Boron-based phosphodiesterase inhibitors show novel binding of boron to PDE4 bimetal center.
Article Details
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Freund YR, Akama T, Alley MR, Antunes J, Dong C, Jarnagin K, Kimura R, Nieman JA, Maples KR, Plattner JJ, Rock F, Sharma R, Singh R, Sanders V, Zhou Y
Boron-based phosphodiesterase inhibitors show novel binding of boron to PDE4 bimetal center.
FEBS Lett. 2012 Sep 21;586(19):3410-4. doi: 10.1016/j.febslet.2012.07.058. Epub 2012 Jul 25.
- PubMed ID
- 22841723 [ View in PubMed]
- Abstract
We have used boron-based molecules to create novel, competitive, reversible inhibitors of phosphodiesterase 4 (PDE4). The co-crystal structure reveals a binding configuration which is unique compared to classical catechol PDE4 inhibitors, with boron binding to the activated water in the bimetal center. These phenoxybenzoxaboroles can be optimized to generate submicromolar potency enzyme inhibitors, which inhibit TNF-alpha, IL-2, IFN-gamma, IL-5 and IL-10 activities in vitro and show safety and efficacy for topical treatment of human psoriasis. They provide a valuable new route for creating novel potent anti-PDE4 inhibitors.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Crisaborole cAMP-specific 3',5'-cyclic phosphodiesterase 4A Protein Humans UnknownInhibitorDetails Crisaborole cAMP-specific 3',5'-cyclic phosphodiesterase 4B Protein Humans UnknownInhibitorDetails Crisaborole cAMP-specific 3',5'-cyclic phosphodiesterase 4C Protein Humans UnknownInhibitorDetails Crisaborole cAMP-specific 3',5'-cyclic phosphodiesterase 4D Protein Humans UnknownInhibitorDetails