5l0b

Crystal Structure of Autotaxin and Compound 1

spinqualitylabelsall models 5l0b, resolution 2.41Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5l0b is a 2 chain structure with sequence from Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.41Å Ligands: 6ZM, BMA, CL, MAN, NAG, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ENPP2_RAT Publication Abstract from PubMed In an effort to develop a novel therapeutic agent aimed at addressing the unmet need of patients with osteoarthritis pain, we set out to develop an inhibitor for autotaxin with excellent potency and physical properties to allow for the clinical investigation of autotaxin-induced nociceptive and neuropathic pain. An initial hit identification campaign led to an aminopyrimidine series with an autotaxin IC50 of 500 nM. X-ray crystallography enabled the optimization to a lead compound that demonstrated favorable potency (IC50 = 2 nM), PK properties, and a robust PK/PD relationship. Novel Autotaxin Inhibitors for the Treatment of Osteoarthritis Pain: Lead Optimization via Structure-Based Drug Design.,Jones SB, Pfeifer LA, Bleisch TJ, Beauchamp TJ, Durbin JD, Klimkowski VJ, Hughes NE, Rito CJ, Dao Y, Gruber JM, Bui H, Chambers MG, Chandrasekhar S, Lin C, McCann DJ, Mudra DR, Oskins JL, Swearingen CA, Thirunavukkarasu K, Norman BH ACS Med Chem Lett. 2016 Aug 2;7(9):857-61. doi: 10.1021/acsmedchemlett.6b00207., eCollection 2016 Sep 8. PMID:27660691 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ectonucleotide pyrophosphatase/phosphodiesterase 3D structures

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