Pfizer World Wide Research and Development, Ramsgate Road, Sandwich, CT13 9NJ, UK; BioTherapeutics Research and Development, Pfizer, Cambridge, MA, 02140, USA.
Chem Biol Drug Des. 2013 Nov;82(5):500-5. doi: 10.1111/cbdd.12169.
The first example of an inhibitor of the kinase TAK1 that binds in the DFG-out conformation is disclosed. These preliminary studies used kinase-targeted screening and structure-based drug design to create a molecule with dual pharmacological inhibition of p38 and TAK1 that demonstrated significant activity in a cell-based, anti-inflammatory assay.
首次揭示了一种结合在 DFG-out 构象中的 TAK1 激酶抑制剂的实例。这些初步研究使用激酶靶向筛选和基于结构的药物设计，创建了一种具有双重药理学抑制 p38 和 TAK1 的分子，该分子在基于细胞的抗炎测定中表现出显著的活性。
