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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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.