| Structural highlights
Publication Abstract from PubMed
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.
Boron-based phosphodiesterase inhibitors show novel binding of boron to PDE4 bimetal center.,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 FEBS Lett. 2012 Sep 21;586(19):3410-4. doi: 10.1016/j.febslet.2012.07.058. Epub, 2012 Jul 25. PMID:22841723[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
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References
- ↑ 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. PMID:22841723 doi:http://dx.doi.org/10.1016/j.febslet.2012.07.058
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