5L0K

Crystal Structure of Autotaxin and Compound PF-8380

5L0K の概要

• エントリーDOI: 10.2210/pdb5l0k/pdb
• 関連するPDBエントリー: 5L0B 5L0E
• 分子名称: Ectonucleotide pyrophosphatase/phosphodiesterase family member 2, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (9 entities in total)
• 機能のキーワード: phospholipase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Rattus norvegicus (Rat)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 188869.98

構造登録者

Durbin, J.D. (登録日: 2016-07-27, 公開日: 2016-08-10, 最終更新日: 2024-11-13)

主引用文献

Jones, S.B.,Pfeifer, L.A.,Bleisch, T.J.,Beauchamp, T.J.,Durbin, J.D.,Klimkowski, V.J.,Hughes, N.E.,Rito, C.J.,Dao, Y.,Gruber, J.M.,Bui, H.,Chambers, M.G.,Chandrasekhar, S.,Lin, C.,McCann, D.J.,Mudra, D.R.,Oskins, J.L.,Swearingen, C.A.,Thirunavukkarasu, K.,Norman, B.H.
Novel Autotaxin Inhibitors for the Treatment of Osteoarthritis Pain: Lead Optimization via Structure-Based Drug Design.
Acs Med.Chem.Lett., 7:857-861, 2016

PubMed 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.

PubMed: 27660691
DOI: 10.1021/acsmedchemlett.6b00207

実験手法

X-RAY DIFFRACTION (2.73 Å)