Inhibitors of interleukin-1 receptor-associated kinase 4 (IRAK4): a patent review (2012-2015).
BACKGROUND
IRAK4 is located proximal to TLR/IL-1 receptors, and in preclinical studies, inhibits downstream signaling from these receptors. The development of novel small molecule inhibitors of this kinase has the potential to lead to new therapeutics to treat diseases such as rheumatoid arthritis, lupus, and lymphomas.


METHODS
The aim of this review is to summarize the recent patent literature (2012-2015) surrounding small molecule inhibitors of IRAK4. Specific examples of the chemical matter from each patent will be discussed, including any data that are presented for the examples highlighted.


CONCLUSIONS
There are currently many examples of highly potent and kinase selective IRAK4 inhibitors and some have been tested in various in vivo disease models, demonstrating robust pre-clinical efficacy. Several compounds appear to have the 'drug-like' properties to advance to the clinic, with Pfizer having already initiated several phase I studies.
a Discovery Chemistry , Merck Sharp and Dohme Corp ., Kenilworth , NJ , USA.
W Michael
WM
Seganish
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000201:enzymology; D015195:Drug Design; D006801:Humans; D053592:Interleukin-1 Receptor-Associated Kinases / Q000037:antagonists & inhibitors*; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy / Q000201:enzymology; D008223:Lymphoma / Q000188:drug therapy / Q000201:enzymology; D010330:Patents as Topic; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects
D047428:Protein Kinase Inhibitors; D053592:Interleukin-1 Receptor-Associated Kinases
IL-R signaling; IRAK4; PF-06650833; TLR signaling; inflammation; serine-threonine kinase inhibitor