Recent advances in the discovery of small molecule inhibitors of interleukin-1 receptor-associated kinase 4 (IRAK4) as a therapeutic target for inflammation and oncology disorders

Divya Chaudhary; Shaughnessy Robinson; Donna L Romero

doi:10.1021/jm5016044

Recent advances in the discovery of small molecule inhibitors of interleukin-1 receptor-associated kinase 4 (IRAK4) as a therapeutic target for inflammation and oncology disorders

J Med Chem. 2015 Jan 8;58(1):96-110. doi: 10.1021/jm5016044. Epub 2014 Dec 5.

Authors

Divya Chaudhary¹, Shaughnessy Robinson, Donna L Romero

Affiliation

¹ Nimbus Discovery , 25 First Street, Suite 404, Cambridge, Massachusetts 02141, United States.

PMID: 25479567
DOI: 10.1021/jm5016044

Abstract

IRAK4, a serine/threonine kinase, plays a key role in both inflammation and oncology diseases. Herein, we summarize the compelling biology surrounding the IRAK4 signaling node in disease, review key structural features of IRAK4 including selectivity challenges, and describe efforts to discover clinically viable IRAK4 inhibitors. Finally, a view of knowledge gained and remaining challenges is provided.

Publication types

Review

MeSH terms

Drug Discovery / methods
Drug Discovery / trends
Humans
Inflammation / drug therapy
Interleukin-1 Receptor-Associated Kinases / antagonists & inhibitors
Interleukin-1 Receptor-Associated Kinases / chemistry*
Interleukin-1 Receptor-Associated Kinases / metabolism
Molecular Structure
Neoplasms / drug therapy
Protein Kinase Inhibitors / chemistry*
Protein Kinase Inhibitors / metabolism
Protein Kinase Inhibitors / pharmacology
Protein Structure, Tertiary*
Signal Transduction / drug effects
Small Molecule Libraries / chemistry*
Small Molecule Libraries / metabolism
Small Molecule Libraries / pharmacology

Substances

Protein Kinase Inhibitors
Small Molecule Libraries
IRAK4 protein, human
Interleukin-1 Receptor-Associated Kinases