2. Signaling Pathways
  3. Immunology/Inflammation
  4. IRAK

IRAK

Interleukin-1 receptor associated kinase; IL-1R associated kinase

IRAK

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Interleukin-1 receptor-associated kinases (IRAKs), are serine/threonine kinases, play critical roles in initiating innate immune responses against foreign pathogens and other types of dangers through their role in Toll-like receptor (TLR) and interleukin 1 receptor (IL-1R) mediated signaling pathways. The four different IRAK-like molecules have been identified: two active kinases, IRAK-1 and IRAK-4, and two inactive kinases, IRAK-2 and IRAK-M. All IRAKs mediate activation of nuclear factor-kappaB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways.

Toll-like receptors transduce their signals through the adaptor molecule MyD88 and members of the IL-1R-associated kinase family (IRAK-1, 2, M and 4). IRAK-1 and IRAK-2, known to form Myddosomes with MyD88-IRAK-4, mediate TLR7-induced TAK1-dependent NF-κB activation. IRAK-M is known to function as a negative regulator that prevents the dissociation of IRAKs from MyD88, thereby inhibiting downstream signalling.

IRAK Isoform Specific Products:

IRAK Isoform Comparison
Cat. No. Product Name Effect Purity Chemical Structure
  • HY-143486
    IRAK4-IN-10
    		Inhibitor
    IRAK4-IN-10 (compound 75) is a potent IRAK4 inhibitor with an IC50 of 1.5 nM. IRAK4-IN-10 blocks MyD88 dependent signaling. IRAK4-IN-9 has the potential for the research of inflammatory diseases, autoimmune diseases, and cancer.
    IRAK4-IN-10
  • HY-146111
    IRAK4-IN-13
    		Inhibitor
    IRAK4-IN-13 (compound 21) is a potent and selective IRAK4 inhibitor with an IC50 of 0.6 nM. IRAK4-IN-13 shows high metabolic clearance with human liver microsomes (HLM) intrinsic clearance is 96 µL/min/mg.
    IRAK4-IN-13
  • HY-175022
    PROTAC IRAK4 degrader-13
    		Degrader
    PROTAC IRAK4 degrader-13 (Degrader 1) is a selective IRAK4 PROTAC degrader with DC50s of 0.86 and 1.1 nM for monocytes and lymphocytes in PBMCs, respectively. PROTAC IRAK4 degrader-13 significantly induces TIR signal activation, and inhibits the expression of circulating proinflammatory cytokines in Imiquimod (HY-B0180) induced psoriasis mice model. PROTAC IRAK4 degrader-13 can be used for TLR- and IL-1R-driven driven neutrophilic inflammation diseases like hidradenitis suppurativa (HS) and atopic dermatitis (AD) research. Pink: IRAK4 ligand; Blue: E3 ligase ligand; Black: linker
    PROTAC IRAK4 degrader-13
  • HY-176197
    IRAK4-IN-31
    		Inhibitor
    IRAK4-IN-31 (Compound II) is a crystalline IRAK4 inhibitor. IRAK4-IN-31 can be used in myelodysplastic syndrome (MDS) research.
    IRAK4-IN-31
  • HY-160654
    IRAK4 modulator-1
    		Modulator
    IRAK4 modulator-1 (example 161) is a modulator of IRAK4 with IC50=4.647 μM. IRAK4 modulator-1 can be used to study IRAK-mediated disorders.
    IRAK4 modulator-1
  • HY-169057
    BI1543673
    		Inhibitor
    BI1543673 is an interleukin-1 receptor-associated kinase 4 (IRAK4) inhibitor. BI1543673 can reduce the inflammatory response stimulated by TLR4 and TLR7/8 in human lung tissue. BI1543673 can decrease inflammatory signaling in a mouse model of lung inflammation induced by LPS.
    BI1543673
  • HY-161620
    DW18134
    		Inhibitor
    DW18134 is an inhibitor for interleukin receptor-associated kinase 4 (IRAK 4) with an IC50 of 11.2 nM. DW18134 inhibits phosphorylation of IRAK4 and IKK, downregulates the secretion of TNF-α and IL-6. DW18134 attenuates the Lipopolysaccharides (HY-D1056)-induced peritonitis and DSS-induced colitis in mouse models, and protects the intestinal barrier function .
    DW18134
  • HY-135382
    PROTAC IRAK4 degrader-2
    		Inhibitor
    PROTAC IRAK4 degrader-2 (Compound 9) is a PROTAC-based IRAK4 degrader that affords potent IRAK4 degradation with a DC50 in peripheral blood mononuclear cells (PBMCs) cells of 151 nM. PROTAC IRAK4 degrader-2 induce a reduction of IRAK4 protein levels with a DC50 of 36 nM in PBMC cells. PROTAC IRAK4 degrader-2 also leads to the inhibition of multiple cytokines in PBMCs.
    PROTAC IRAK4 degrader-2
  • HY-148277
    KTX-612
    KTX-612 is an orally active IRAK4 PROTAC degrader with a DC50 value of 7 nM. KTX-612 can be used for the research of oncology.(Pink:IRAK4 inhibitor (HY-150735); Black: linker; Blue: CRBN Ligand (HY-10984))
    KTX-612
  • HY-162641
    AF-45
    		Inhibitor
    AF-45 inhibits IRAK4 and IRAK1, with IC50s of 128 nM and 1765 nM. AF-45 inhibits the release of IL-6 and TNF-α in macrophages, with IC50s of 0.53-1.54 μM and 0.6-2.75 μM. AF-45 is also an inhibitor for NF-κB/MAPK signaling pathway. AF-45 exhibits anti-inflammatory activities against DSS-induced ulcerative colitis and Lipopolysaccharide (HY-D1056)-induced acute lung injury in mouse model. AF-45 exhibits good pharmacokinetic characteristics in rat models.
    AF-45
  • HY-172591
    IRAK4 ligand-13
    		Ligand
    IRAK4 ligand-13 is a IRAK4 ligand. IRAK4 ligand-13 is a ligand for Target Protein for PROTAC. IRAK4 ligand-13 can be used for synthesis of PROTACs, such as LZ-07 (HY-172591).
    IRAK4 ligand-13
  • HY-158374
    BIO-8169
    		Inhibitor
    BIO-8169 is a selective inhibitor for interleukin receptor-associated kinase 4 (IRAK 4), with an IC50 of 0.23 nM. BIO-8169 exhibits good pharmacokinetic character, reduces the production of pro-inflammatory cytokines, and attenuates the autoimmune encephalomyelitis in EAE mice model. BIO-8169 exhibits good blood brain penetrant with a rat Kpu,u of 0.7.
    BIO-8169
  • HY-139315
    PROTAC IRAK4 degrader-4
    		Inhibitor
    PROTAC IRAK4 degrader-4 is a Cereblon-based PROTAC as interleukin-1 receptor-associated kinase 4 (IRAK4) degrader extracted from patent US20190192668A1, compound I-127.
    PROTAC IRAK4 degrader-4
  • HY-162359
    BIO-7488
    		Inhibitor 99.44%
    BIO-7488 is a potent, selective, oral active and CNS-penetrant IRAK4 inhibitor with the IC50 of 0.6 nM and > 30 μM for IRAK4 and hERG, respectively.
    BIO-7488
  • HY-158434
    IRAK1-IN-1
    		Inhibitor
    IRAK1-IN-1 (compound B8) is an orally active IRAK1 inhibitor. IRAK1-IN-1 inhibits the release of IL-6 with the IC50 values of 4.57 μM and 6.51 μM on mouse cells J774A. 1 and human cells THP-1, respectively. IRAK1-IN-1 alleviats LPS (HY-D1056)-induced acute lung injury (ALI) and DSS(HY-116282C)-induced colitis in mice.
    IRAK1-IN-1
  • HY-172406
    MAPK-IN-4
    		Ligand
    MAPK-IN-4 (Compound c1) is an orally active anti-inflammatory agent. MAPK-IN-4 can inhibit the expression and release of pro-inflammatory cytokines IL-6 and TNF-α induced by LPS (HY-D1056). MAPK-IN-4 can bind to IRAK4 and exert its anti-inflammatory effect by inhibiting the MAPK pathway.
    MAPK-IN-4
  • HY-148276
    KTX-497
    KTX-497 is an IRAK4 PROTAC degrader with a DC50 value of 3 nM. KTX-497 can be used for the research of oncology.(Pink:IRAK4 inhibitor (HY-150735); Black: linker; Blue: CRBN Ligand (HY-10984))
    KTX-497
  • HY-148275
    KTX-955
    		Inhibitor
    KTX-955 is an antumor and effective IRAK4 degrader, with DC50 values of 5 nM and 130 nM for IRAK4 and Ikaros, respectively. KTX-955 is composed of CRBN ligand (blue part) Pomalidomide (HY-10984) and target protein ligand (red part) IRAK4-IN-20 (HY-150735).
    KTX-955
  • HY-155132
    IRAK4-IN-28
    		Inhibitor
    IRAK4-IN-28 (compound 42) is an orally active IRAK4 inhibitor (IC50=8.9 nM). IRAK4-IN-28 has binding affinity for IRAK4 with a Kd of 0.58 nM. IRAK4-IN-28 can be used in the research of inflammation and autoimmune diseases.
    IRAK4-IN-28
  • HY-146113
    IRAK4-IN-15
    		Inhibitor
    IRAK4-IN-15 (compound 35) is a potent and selective IRAK4 inhibitor with an IC50 of 0.002 µM. IRAK4-IN-15 shows good human PK predictions with low intrinsic clearance. IRAK4-IN-15 shows great synergistic in vitro activity against MyD88/CD79 double mutant ABC-DLBCL in combination with Acalabrutinib. .
    IRAK4-IN-15
Cat. No. Product Name / Synonyms Application Reactivity
IRAK Isoform Comparison

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