6b96 | pdb_00006b96

Crystal Structure of PDE2 in complex with compound 16

spinqualitylabelsall models 6b96, resolution 1.88Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6b96 is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CZV, EDO, MG, ZN Activity: 3',5'-cyclic-nucleotide phosphodiesterase, with EC number 3.1.4.17 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [PDE2A_HUMAN] Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes. Publication Abstract from PubMed We have identified a novel PDE2 inhibitor series using fragment-based screening. Pyrazolopyrimidine fragment 1, while possessing weak potency (Ki=22.4muM), exhibited good binding efficiencies (LBE=0.49, LLE=4.48) to serve as a start for structure-based drug design. With the assistance of molecular modeling and X-ray crystallography, this fragment was developed into a series of potent PDE2 inhibitors with good physicochemical properties. Compound 16, a PDE2 selective inhibitor, was identified that exhibited favorable rat pharmacokinetic properties. The identification of a novel lead class for phosphodiesterase 2 inhibition by fragment-based drug design.,Forster AB, Abeywickrema P, Bunda J, Cox CD, Cabalu TD, Egbertson M, Fay J, Getty K, Hall D, Kornienko M, Lu J, Parthasarathy G, Reid J, Sharma S, Shipe WD, Smith SM, Soisson S, Stachel SJ, Su HP, Wang D, Berger R Bioorg Med Chem Lett. 2017 Dec 1;27(23):5167-5171. doi:, 10.1016/j.bmcl.2017.10.054. Epub 2017 Oct 23. PMID:29113762 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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