First comprehensive structural and biophysical analysis of MAPK13 inhibitors targeting DFG-in and DFG-out binding modes

• Published in: Biochimica et biophysica acta Vol. 1860; no. 11; pp. 2335 - 2344
• Main Authors: Yurtsever, Zeynep, Patel, Dhara A., Kober, Daniel L., Su, Alvin, Miller, Chantel A., Romero, Arthur G., Holtzman, Michael J., Brett, Tom J.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.11.2016; Elsevier
• Subjects: BASIC BIOLOGICAL SCIENCES; Binding Sites; Chronic inflammatory lung disease; crystal structure; Differential scanning fluorimetry; half life; Humans; hydrogen bonding; Inhibitor half-lives; inhibitory concentration 50; interferometry; Kinase inhibitor; mitogen-activated protein kinase; Mitogen-Activated Protein Kinase 13 - antagonists & inhibitors; Mitogen-Activated Protein Kinase 13 - chemistry; Mitogen-Activated Protein Kinase 13 - metabolism; p38 kinase; pharmacokinetics; Protein Binding; Protein Kinase Inhibitors - chemistry; Protein Kinase Inhibitors - pharmacology; Quantitative Structure-Activity Relationship; Structure-based drug design; p38 kinase; Structure-based drug design; Differential scanning fluorimetry; Chronic inflammatory lung disease; Kinase inhibitor; Inhibitor half-lives

P38 MAP kinases are centrally involved in mediating extracellular signaling in various diseases. While much attention has previously been focused on the ubiquitously expressed family member MAPK14 (p38α), recent studies indicate that family members such as MAPK13 (p38δ) display a more selective cell...