Fragment-based drug discovery of potent and selective MKK3/6 inhibitors.
Basic Information
ID: ALA3745714
Journal: Bioorg Med Chem Lett
Title: Fragment-based drug discovery of potent and selective MKK3/6 inhibitors.
Authors: Adams M, Kobayashi T, Lawson JD, Saitoh M, Shimokawa K, Bigi SV, Hixon MS, Smith CR, Tatamiya T, Goto M, Russo J, Grimshaw CE, Swann S.
Abstract: The MAPK signaling cascade, comprised of several linear and intersecting pathways, propagates signaling into the nucleus resulting in cytokine and chemokine release. The Map Kinase Kinase isoforms 3 and 6 (MKK3 and MKK6) are responsible for the phosphorylation and activation of p38, and are hypothesized to play a key role in regulating this pathway without the redundancy seen in downstream effectors. Using FBDD, we have discovered efficient and selective inhibitors of MKK3 and MKK6 that can serve as tool molecules to help further understand the role of these kinases in MAPK signaling, and the potential impact of inhibiting kinases upstream of p38.
CiteXplore: 26704264
DOI: 10.1016/j.bmcl.2015.11.054
Patent ID: ┄