5eak

Optimization of Microtubule Affinity Regulating Kinase (MARK) Inhibitors with Improved Physical PropertiesOptimization of Microtubule Affinity Regulating Kinase (MARK) Inhibitors with Improved Physical Properties

Structural highlights 5eak is a 2 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 2.8Å Ligands: Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function MARK2_HUMAN Publication Abstract from PubMed Inhibition of microtubule affinity regulating kinase (MARK) represents a potentially attractive means of arresting neurofibrillary tangle pathology in Alzheimer's disease. This manuscript outlines efforts to optimize a pyrazolopyrimidine series of MARK inhibitors by focusing on improvements in potency, physical properties and attributes amenable to CNS penetration. A unique cylcyclohexyldiamine scaffold was identified that led to remarkable improvements in potency, opening up opportunities to reduce MW, Pgp efflux and improve pharmacokinetic properties while also conferring improved solubility. Optimization of microtubule affinity regulating kinase (MARK) inhibitors with improved physical properties.,Sloman DL, Noucti N, Altman MD, Chen D, Mislak AC, Szewczak A, Hayashi M, Warren L, Dellovade T, Wu Z, Marcus J, Walker D, Su HP, Edavettal SC, Munshi S, Hutton M, Nuthall H, Stanton MG Bioorg Med Chem Lett. 2016 Sep 1;26(17):4362-6. doi: 10.1016/j.bmcl.2016.02.003. , Epub 2016 Feb 6. PMID:27491711 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Serine/threonine protein kinase 3D structures

spinqualitylabelsall models 5eak, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image