| Structural highlights
4kp6 is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , , |
| Gene: | DPDE4, PDE4B (HUMAN) |
| Activity: | 3',5'-cyclic-nucleotide phosphodiesterase, with EC number 3.1.4.17 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[PDE4B_HUMAN] Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. May be involved in mediating central nervous system effects of therapeutic agents ranging from antidepressants to antiasthmatic and anti-inflammatory agents.[1] [2]
Publication Abstract from PubMed
Expanding on HTS hit 4 afforded a series of [1,3,5]triazine derivatives as novel PDE4 inhibitors. The SAR development and optimization process with the emphasis on ligand efficiency and physicochemical properties led to the discovery of compound 44 as a potent, selective and orally active PDE4 inhibitor.
Discovery of triazines as potent, selective and orally active PDE4 inhibitors.,Gewald R, Grunwald C, Egerland U Bioorg Med Chem Lett. 2013 Aug 1;23(15):4308-14. doi: 10.1016/j.bmcl.2013.05.099., Epub 2013 Jun 10. PMID:23806553[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Xu RX, Hassell AM, Vanderwall D, Lambert MH, Holmes WD, Luther MA, Rocque WJ, Milburn MV, Zhao Y, Ke H, Nolte RT. Atomic structure of PDE4: insights into phosphodiesterase mechanism and specificity. Science. 2000 Jun 9;288(5472):1822-5. PMID:10846163
- ↑ Xu RX, Rocque WJ, Lambert MH, Vanderwall DE, Luther MA, Nolte RT. Crystal structures of the catalytic domain of phosphodiesterase 4B complexed with AMP, 8-Br-AMP, and rolipram. J Mol Biol. 2004 Mar 19;337(2):355-65. PMID:15003452 doi:http://dx.doi.org/10.1016/j.jmb.2004.01.040
- ↑ Gewald R, Grunwald C, Egerland U. Discovery of triazines as potent, selective and orally active PDE4 inhibitors. Bioorg Med Chem Lett. 2013 Aug 1;23(15):4308-14. doi: 10.1016/j.bmcl.2013.05.099., Epub 2013 Jun 10. PMID:23806553 doi:10.1016/j.bmcl.2013.05.099
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