The various cells of innate immune system quickly counter-attack invading pathogens, and mount up "first line" defense through their trans-membrane receptors including Toll-like receptors (TLRs) and interleukin receptors (IL-Rs) that result in the secretion of pro-inflammatory cytokines. Albeit such inflammatory responses are beneficial in pathological conditions, their overstimulation may cause severe inflammatory damage thus, make this defense system a "double edged sword". IRAK-4 has been evaluated as an indispensable element of IL-Rs and TLR pathways that can regulate the abnormal levels of cytokines, and therefore could be employed to manage immune- and inflammation-related disorders. Historically, the identification of selective and potent inhibitors has been challenging; thus, a limited number of small molecule IRAK-4 inhibitors are available in literature. Recently, IRAK-4 achieved great attention, when Ligand® pharmaceutical and Nimbus Discovery® reported the beneficial potentials of IRAK-4 inhibitors in the pre-clinical evaluation for various inflammatory- and immune-related disorders, but not limited to, such as rheumatoid arthritis, inflammatory bowel disease, psoriasis, gout, asthma and cancer.
|Number of pages||17|
|State||Published - 1 Jun 2015|
Bibliographical noteFunding Information:
The authors express their gratitude to the Indian Council of Medical Research (ICMR), New Delhi for providing Senior Research Fellowship (SRF; Project No. 45/3/2012-BMS/BIF) to Mr. Malkeet Singh Bahia, a Ph.D. Research Scholar in the Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab, India.
© 2015 Elsevier Inc.
- Interleukin-1 receptor associated kinase-4 (IRAK-4)
- MyD88-dependent and independent pathways
- TLR/IL-1 receptor (TIR) superfamily
- Toll-like receptors