| Title : Chemical genetics screening reveals KIAA1363 as a cytokine-lowering target - Hunerdosse_2014_ACS.Chem.Biol_9_2905 |
| Author(s) : Hunerdosse DM , Morris PJ , Miyamoto DK , Fisher KJ , Bateman LA , Ghazaleh JR , Zhong S , Nomura DK |
| Ref : ACS Chemical Biology , 9 :2905 , 2014 |
| Abstract : Inflammation is a hallmark of many human diseases, including pain, arthritis, atherosclerosis, obesity and diabetes, cancer, and neurodegenerative diseases. Although there are several successfully marketed small molecules anti-inflammatory drugs such as cyclooxygenase inhibitors and glucocorticoids, many of these compounds are also associated with various adverse cardiovascular or immunosuppressive side effects. Thus, identifying novel anti-inflammatory small molecules and their targets is critical for developing safer and more effective next-generation treatment strategies for inflammatory diseases. Here, we have conducted a chemical genetics screen to identify small molecules that suppress the release of the inflammatory cytokine TNFalpha from stimulated macrophages. We have used an enzyme class-directed chemical library for our screening efforts to facilitate subsequent target identification using activity-based protein profiling (ABPP). Using this strategy, we have found that KIAA1363 is a novel target for lowering key pro-inflammatory cytokines through affecting key ether lipid metabolism pathways. Our study highlights the application of combining chemical genetics with chemoproteomic and metabolomic approaches toward identifying and characterizing anti-inflammatory smal molecules and their targets. |
| ESTHER : Hunerdosse_2014_ACS.Chem.Biol_9_2905 |
| PubMedSearch : Hunerdosse_2014_ACS.Chem.Biol_9_2905 |
| PubMedID: 25343321 |
| Gene_locus related to this paper: human-NCEH1 |
| Gene_locus related to this paper: human-NCEH1 |
Hunerdosse DM, Morris PJ, Miyamoto DK, Fisher KJ, Bateman LA, Ghazaleh JR, Zhong S, Nomura DK (2014)
Chemical genetics screening reveals KIAA1363 as a cytokine-lowering target
ACS Chemical Biology
9 :2905
Hunerdosse DM, Morris PJ, Miyamoto DK, Fisher KJ, Bateman LA, Ghazaleh JR, Zhong S, Nomura DK (2014)
ACS Chemical Biology
9 :2905