Bing Dai
Tufts University
KinaseChemistryRegorafenibRIPK2Protein kinase A
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Publications 4
#1Chalada Suebsuwong (UH: University of Houston)H-Index: 5
#2Bing Dai (Tufts University)H-Index: 2
Last. Alex N. Bullock (SGC: Structural Genomics Consortium)H-Index: 40
view all 12 authors...
Abstract Receptor-interacting protein kinase 2 (RIPK2) is a key mediator of nucleotide-binding oligomerization domain (NOD) cell signaling that has been implicated in various chronic inflammatory conditions. A new class of RIPK2 kinase/NOD signaling inhibitors based on a 3,5-diphenyl-2-aminopyridine scaffold was developed. Several co-crystal structures of RIPK2•inhibitor complexes were analyzed to provide insights into inhibitor selectivity versus the structurally related activin receptor-like k...
#1Matous Hrdinka (Ludwig Institute for Cancer Research)H-Index: 12
#2Lisa Schlicher (Ludwig Institute for Cancer Research)H-Index: 1
Last. Mads Gyrd-Hansen (Ludwig Institute for Cancer Research)H-Index: 26
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Abstract RIPK2 mediates inflammatory signaling by the bacteria‐sensing receptors NOD1 and NOD2. Kinase inhibitors targeting RIPK2 are a proposed strategy to ameliorate NOD‐mediated pathologies. Here, we reveal that RIPK2 kinase activity is dispensable for NOD2 inflammatory signaling and show that RIPK2 inhibitors function instead by antagonizing XIAP‐binding and XIAP‐mediated ubiquitination of RIPK2. We map the XIAP binding site on RIPK2 to the loop between β2 and β3 of the N‐lobe of the kinase,...
8 CitationsSource
#1Daniel M. PinkasH-Index: 9
#2Joshua C. BuftonH-Index: 4
Last. Alex N. BullockH-Index: 40
view all 14 authors...
#1Chalada Suebsuwong (UH: University of Houston)H-Index: 5
#2Daniel M. Pinkas (SGC: Structural Genomics Consortium)H-Index: 9
Last. Gregory D. Cuny (UH: University of Houston)H-Index: 41
view all 8 authors...
Abstract Development of selective kinase inhibitors remains a challenge due to considerable amino acid sequence similarity among family members particularly in the ATP binding site. Targeting the activation loop might offer improved inhibitor selectivity since this region of kinases is less conserved. However, the strategy presents difficulties due to activation loop flexibility. Herein, we report the design of receptor-interacting protein kinase 2 (RIPK2) inhibitors based on pan-kinase inhibito...
2 CitationsSource