Recent Advances in IRAK1: Pharmacological and Therapeutic Aspects

被引:10
作者
Kim, Kyeong Min [1 ]
Hwang, Na-Hee [1 ]
Hyun, Ja-Shil [1 ]
Shin, Dongyun [1 ]
机构
[1] Gachon Univ, Coll Pharm, Hambakmoe Ro 191, Incheon 21935, South Korea
基金
新加坡国家研究基金会;
关键词
interleukin receptor-associated kinase (IRAK) proteins; inhibitor; degrader; immunity; SIGNALING MEDIATOR; KINASE IRAK; INNATE; ACTIVATION; INFLAMMATION; INHIBITORS; FAMILY; NEUROINFLAMMATION; IDENTIFICATION; MICRORNA-146A;
D O I
10.3390/molecules29102226
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Interleukin receptor-associated kinase (IRAK) proteins are pivotal in interleukin-1 and Toll-like receptor-mediated signaling pathways. They play essential roles in innate immunity and inflammation. This review analyzes and discusses the physiological functions of IRAK1 and its associated diseases. IRAK1 is involved in a wide range of diseases such as dry eye, which highlights its potential as a therapeutic target under various conditions. Various IRAK1 inhibitors, including Pacritinib and Rosoxacin, show therapeutic potential against malignancies and inflammatory diseases. The covalent IRAK1 inhibitor JH-X-119-01 shows promise in B-cell lymphomas, emphasizing the significance of covalent bonds in its activity. Additionally, the emergence of selective IRAK1 degraders, such as JNJ-101, provides a novel strategy by targeting the scaffolding function of IRAK1. Thus, the evolving landscape of IRAK1-targeted approaches provides promising avenues for increasingly safe and effective therapeutic interventions for various diseases.
引用
收藏
页数:17
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[11]   Pacritinib Inhibition of IRAK1 Blocks Aberrant TLR8 Signalling by SARS-CoV-2 and HIV-1-Derived RNA [J].
Campbell, Grant R. ;
Rawat, Pratima ;
Spector, Stephen A. .
JOURNAL OF INNATE IMMUNITY, 2023, 15 (01) :96-106
[12]   Different Innate and Adaptive Immune Responses to SARS-CoV-2 Infection of Asymptomatic, Mild, and Severe Cases [J].
Carsetti, Rita ;
Zaffina, Salvatore ;
Mortari, Eva Piano ;
Terreri, Sara ;
Corrente, Francesco ;
Capponi, Claudia ;
Palomba, Patrizia ;
Mirabella, Mattia ;
Cascioli, Simona ;
Palange, Paolo ;
Cuccaro, Ilaria ;
Milito, Cinzia ;
Zumla, Alimuddin ;
Maeurer, Markus ;
Camisa, Vincenzo ;
Vinci, Maria Rosaria ;
Santoro, Annapaola ;
Cimini, Eleonora ;
Marchioni, Luisa ;
Nicastri, Emanuele ;
Palmieri, Fabrizio ;
Agrati, Chiara ;
Ippolito, Giuseppe ;
Porzio, Ottavia ;
Concato, Carlo ;
Muda, Andrea Onetti ;
Raponi, Massimiliano ;
Quintarelli, Concetta ;
Quinti, Isabella ;
Locatelli, Franco .
FRONTIERS IN IMMUNOLOGY, 2020, 11
[13]   IRAK1-Dependent Signaling Mediates Mortality in Polymicrobial Sepsis [J].
Chandra, Rachna ;
Federici, Stephanie ;
Bishwas, Tripti ;
Nemeth, Zoltan H. ;
Deitch, Edwin A. ;
Thomas, James A. ;
Spolarics, Zoltan .
INFLAMMATION, 2013, 36 (06) :1503-1512
[14]   Downregulation of IRAK1 Prevents the Malignant Behavior of Hepatocellular Carcinoma Cells by Blocking Activation of the MAPKs/NLRP3/IL-1β Pathway [J].
Chen, Wei ;
Wei, Tao ;
Chen, Yinghua ;
Yang, Lan ;
Wu, Xiaomin .
ONCOTARGETS AND THERAPY, 2020, 13 :12787-12796
[15]   Interleukin-1 receptor-associated kinase 4 (IRAK4) plays a dual role in myddosome formation and Toll-like receptor signaling [J].
De Nardo, Dominic ;
Balka, Katherine R. ;
Gloria, Yamel Cardona ;
Rao, Vikram R. ;
Latz, Eicke ;
Masters, Seth L. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2018, 293 (39) :15195-15207
[16]   A Toll-like receptor 2 ligand stimulates Th2 responses in vivo, via induction of extracellular signal-regulated kinase mitogen-activated protein kinase and c-Fos in dendritic cells [J].
Dillon, S ;
Agrawal, A ;
Van Dyke, T ;
Landreth, G ;
McCauley, L ;
Koh, A ;
Maliszewski, C ;
Akira, S ;
Pulendran, B .
JOURNAL OF IMMUNOLOGY, 2004, 172 (08) :4733-4743
[17]   Small molecules targeting the innate immune cGAS-STING-TBK1 signaling pathway [J].
Ding, Chunyong ;
Song, Zilan ;
Shen, Ancheng ;
Chen, Tingting ;
Zhang, Ao .
ACTA PHARMACEUTICA SINICA B, 2020, 10 (12) :2272-2298
[18]   INVITRO ANTI-MICROBIAL ACTIVITY OF ROSOXACIN AGAINST NEISSERIA-GONORRHOEAE, CHLAMYDIA-TRACHOMATIS, AND UREAPLASMA-UREALYTICUM [J].
DOBSON, RA ;
OCONNOR, JR ;
POULIN, SA ;
KUNDSIN, RB ;
SMITH, TF ;
CAME, PE .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1980, 18 (05) :738-740
[19]   Microglia and Astrocytes in Alzheimer's Disease: Implications for Therapy [J].
Fakhoury, Marc .
CURRENT NEUROPHARMACOLOGY, 2018, 16 (05) :508-518
[20]   Cutting Edge: TLR Signaling Licenses IRAK1 for Rapid Activation of the NLRP3 Inflammasome [J].
Fernandes-Alnemri, Teresa ;
Kang, Seokwon ;
Anderson, Connor ;
Sagara, Junji ;
Fitzgerald, Katherine A. ;
Alnemri, Emad S. .
JOURNAL OF IMMUNOLOGY, 2013, 191 (08) :3995-3999