4pm0

PDE7A catalytic domain in complex with 2-(Cyclopentylamino)thieno[3,2-d]pyrimidin-4(3H)-one derivative

spinqualitylabelsall models 4pm0, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4pm0 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.1Å Ligands: 32V, MG, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PDE7A_HUMAN Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. May have a role in muscle signal transduction. Publication Abstract from PubMed The discovery of a new series of potent phosphodiesterase 7 (PDE7) inhibitors is described. Novel thieno[3,2-d]pyrimidin-4(3H)-one hit compounds were identified from our chemical library. Preliminary modifications of the hit compounds were performed, resulting in the discovery of a fragment-sized compound (10) with highly improved ligand efficiency. Compound design was guided by structure-activity relationships and computational modeling. The 6-substituted derivatives of the thienopyrimidinone showed diminished activity and enzyme selectivity. However, synthesis of the 7-substituted derivatives resulted in the discovery of 28e, a desirable lead compound that selectively inhibits PDE7 with single-digit nanomolar potency while displaying potent cellular efficacy. Discovery of 2-(Cyclopentylamino)thieno[3,2-d]pyrimidin-4(3H)-one Derivatives as a New Series of Potent Phosphodiesterase 7 Inhibitors.,Kawai K, Endo Y, Asano T, Amano S, Sawada K, Ueo N, Takahashi N, Sonoda Y, Nagai M, Kamei N, Nagata N J Med Chem. 2014 Nov 19. PMID:25383422 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Phosphodiesterase 3D structures

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