4ia0

Crystal structure of the PDE5A1 catalytic domain in complex with novel inhibitors

spinqualitylabelsall models 4ia0, resolution 2.17Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4ia0 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: 5BB, MG, ZN Related: 4i9z Gene: PDE5, PDE5A (HUMAN) Activity: 3',5'-cyclic-GMP phosphodiesterase, with EC number 3.1.4.35 Resources: FirstGlance, OCA, RCSB, PDBsum Function [PDE5A_HUMAN] Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This phosphodiesterase catalyzes the specific hydrolysis of cGMP to 5'-GMP. Publication Abstract from PubMed The substituents both at the 6-position of the 5-bromopyrimidinone ring and at the 5'-position of the phenyl ring of 5-bromopyrimidin-4(3H)-ones were explored. 5-Bromo-6-isopropyl-2-(2-propoxy-phenyl)pyrimidin-4(3H)-one was identified as a new scaffold for potent PDE5 inhibitors. The crystal structures of PDE5/2e and PDE5/10a complexes provided a structural basis for the inhibition of 5-bromopyrimidinones to PDE5. In addition, it was also found that there is a great tolerance for the substitution at the 5'-position of the phenyl ring of 5-bormopyrimidinones and the resulted compound 13a has the highest inhibition activity to PDE5 (IC50, 1.7 nM). Exploration of the 5-bromopyrimidin-4(3H)-ones as potent inhibitors of PDE5.,Gong X, Wang G, Ren J, Liu Z, Wang Z, Chen T, Yang X, Jiang X, Shen J, Jiang H, Aisa HA, Xu Y, Li J Bioorg Med Chem Lett. 2013 Sep 1;23(17):4944-7. doi: 10.1016/j.bmcl.2013.06.062. , Epub 2013 Jun 29. PMID:23867165 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Phosphodiesterase

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