Basic Information
ID: ALA4431396
Journal: ACS Med Chem Lett
Title: Novel Autotaxin Inhibitors for the Treatment of Osteoarthritis Pain: Lead Optimization via Structure-Based Drug Design.
Authors: 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.
Abstract: 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.
CiteXplore: 27660691
DOI: 10.1021/acsmedchemlett.6b00207
Patent ID: ┄
Associated Items: Associated Bioactivities Associated Assays Associated Compounds Associated Targets