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IRAK inhibitors act on interleukin-1 receptor-associated kinases (IRAKs), kinases of innate immune receptor signaling. IRAK was cloned in 1996 as a serine/threonine kinase that associates with the interleukin-1 (IL-1) receptor after stimulation. Mice lacking IRAK4 showed severe defects in IL-1 and Toll-like receptor signaling, which established a central role for this family member. The adaptor myeloid differentiation primary response 88 (MyD88) recruits IRAK4, which then phosphorylates IRAK1 on the route to nuclear factor kappa B activation. Emavusertib, listed as CA-4948, and IRAK inhibitor 4 target IRAK4, while IRAK-1-4 Inhibitor I blocks both IRAK1 and IRAK4. The list also contains compounds with other targets, such as the c-Jun N-terminal kinase inhibitor JNK-IN-7.
PROTAC IRAK4 ligand-4 is a selective ligand that targets IRAK4, facilitating the degradation of this protein via the PROTAC (proteolysis-targeting chimera) mechanism. This compound exhibits antitumor activity, making it a valuable tool for cancer research. Additionally, it can be utilized to synthesize the PROTAC IRAK4 degrader-12, contributing to the development of targeted therapeutic strategies in oncology.
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PROTAC IRAK4 degrader-12 is a PROTAC compound designed to selectively target and induce the degradation of IRAK4 via the Cereblon E3 ligase pathway. It demonstrates a significant degradation efficacy, achieving a maximum degradation rate of 108.46% in K562 cells with an IC50 of 4.87 nM. This reagent is particularly useful for research applications focused on inflammatory signaling pathways and therapeutic development targeting IRAK4-related diseases.
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IRAK4-IN-9 is a potent inhibitor of IRAK4, demonstrating an IC50 of 1.5 nM. This compound effectively disrupts MyD88-dependent signaling pathways, making it a valuable tool for investigating mechanisms of inflammation and immune response. IRAK4-IN-9 is relevant for research applications in inflammatory diseases, autoimmune disorders, and cancer biology.
IRAK4-IN-10 is a potent inhibitor of IRAK4, exhibiting an IC50 value of 1.5 nM. This compound effectively interrupts MyD88-dependent signaling pathways, making it a valuable tool for studying the molecular mechanisms underlying inflammatory and autoimmune diseases, as well as various cancers. Its ability to target IRAK4 positions IRAK4-IN-10 as a promising reagent for research in related therapeutic fields.
IRAK4-IN-13 is a potent and selective inhibitor of IRAK4 with an IC50 of 0.6 nM. This compound demonstrates significant metabolic clearance, with an intrinsic clearance rate of 96 µL/min/mg in human liver microsomes. IRAK4-IN-13 is useful for studying IRAK4-mediated signaling pathways and evaluating therapeutic strategies in various inflammatory diseases.
IRAK4-IN-31 is a selective inhibitor of IRAK4, a key kinase in the Toll-like receptor signaling pathway. This compound exhibits potent inhibitory activity against IRAK4, making it valuable for studying immune signaling and associated pathways. IRAK4-IN-31 is particularly relevant in research related to myelodysplastic syndromes (MDS) and may aid in elucidating therapeutic strategies for hematological malignancies.
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IRAK4 modulator-1 is a selective modulator of IRAK4, demonstrating an IC50 of 4.647 μM. This compound is instrumental in the exploration of IRAK-mediated signaling pathways, making it a valuable tool for investigating diseases associated with dysregulated inflammation and immune responses. Researchers can utilize IRAK4 modulator-1 to further understand the role of IRAK4 in various pathological conditions.
PROTAC IRAK3 degrader-2 is a potent IRAK3 PROTAC degrader with a DC50 of less than or equal to 50 nM. This compound promotes the ubiquitination and subsequent degradation of the IRAK3 protein, making it a valuable tool for studying immune-related diseases. Its unique design incorporates ligands for E3 ligase and a linker configuration, facilitating targeted degradation and aiding research into therapeutic strategies for modulating immune responses.
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DW18134 is a selective inhibitor of interleukin receptor-associated kinase 4 (IRAK4) with an IC50 of 11.2 nM. It effectively inhibits the phosphorylation of IRAK4 and IKK, leading to downregulated secretion of pro-inflammatory cytokines TNF-α and IL-6. In preclinical studies, DW18134 demonstrates efficacy in mitigating lipopolysaccharide-induced peritonitis and dextran sulfate sodium-induced colitis in mouse models, while also preserving intestinal barrier integrity. This compound is valuable for researching inflammatory pathways and therapeutic strategies in inflammatory bowel disease.
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PROTAC IRAK4 Degrader-2 is a PROTAC-based compound designed to target and degrade IRAK4, displaying potent degradation efficacy with a DC50 value of 151 nM in peripheral blood mononuclear cells (PBMCs). It effectively reduces IRAK4 protein levels, achieving a DC50 of 36 nM in these cells. Additionally, PROTAC IRAK4 Degrader-2 inhibits the production of multiple cytokines, making it a valuable tool for research in inflammation and immune response modulation.
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KTX-612 is an orally bioavailable IRAK4 PROTAC degrader with a DC50 value of 7 nM. This compound is designed to selectively target and promote the degradation of IRAK4, a key protein involved in inflammatory and oncogenic signaling pathways. KTX-612 has potential applications in oncology research, facilitating studies focused on the modulation of IRAK4 and its implications in cancer progression and treatment.
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IRAK4 ligand-13 is a selective ligand targeting IRAK4, a key component in the interleukin-1 receptor and Toll-like receptor signaling pathways. This compound is designed for the development of proteolysis-targeting chimeras (PROTACs), facilitating targeted protein degradation. It is suitable for research applications aimed at modulating immune responses and studying signaling pathways associated with inflammation and cancer.
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BIO-8169 is a selective inhibitor of interleukin receptor-associated kinase 4 (IRAK4) with an IC50 of 0.23 nM. This compound demonstrates significant anti-inflammatory activity by reducing the production of pro-inflammatory cytokines. Additionally, BIO-8169 shows promising pharmacokinetic properties, including effective blood-brain barrier penetration, indicated by a rat Kpu,u of 0.7, making it suitable for investigating autoimmune conditions such as experimental autoimmune encephalomyelitis (EAE).
PROTAC IRAK3 degrader-1 is a potent and selective degrader targeting IRAK3, with an IC50 of 5 nM. This compound effectively facilitates the ubiquitination and subsequent degradation of IRAK3, thereby modulating inflammatory responses. Its primary research applications include studies on innate immunity and the development of targeted therapies for inflammatory diseases.
PROTAC IRAK4 degrader-4 is a Cereblon-based bifunctional molecule designed to degrade interleukin-1 receptor-associated kinase 4 (IRAK4). This compound facilitates targeted protein degradation, leading to effective modulation of IRAK4 levels in cells. Research applications include investigating inflammatory signaling pathways and therapeutic approaches for autoimmune diseases.
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KTX-497 is a potent IRAK4 degrader utilizing the PROTAC technology, exhibiting a DC50 value of 3 nM. This compound effectively targets and degrades IRAK4, making it a valuable tool for oncology research. Its mechanism allows for the selective modulation of signaling pathways implicated in cancer progression, facilitating the exploration of novel therapeutic strategies.
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KTX-955 is a potent IRAK4 degrader that facilitates the targeted degradation of IRAK4 protein. With DC50 values of 5 nM for IRAK4 and 130 nM for Ikaros, this compound demonstrates significant efficacy in modulating signaling pathways involved in tumorigenesis. KTX-955 comprises a CRBN ligand derived from Pomalidomide and a specific ligand targeting IRAK4, making it a valuable tool for research into cancer biology and therapeutic interventions.
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IRAK4-IN-28 is a potent inhibitor of IRAK4, exhibiting an IC50 of 8.9 nM and a binding affinity characterized by a Kd of 0.58 nM. This compound is suitable for studies targeting inflammation and autoimmune diseases, providing valuable insights into the mechanisms of immune response modulation. Its selectivity and potency make it a useful tool for elucidating the role of IRAK4 in various biological processes.
IRAK4-IN-15 is a selective inhibitor of IRAK4, demonstrating a remarkable IC50 of 0.002 µM. This compound exhibits favorable pharmacokinetic predictions in humans with low intrinsic clearance. In vitro studies reveal its potent synergistic activity against MyD88/CD79 double mutant ABC-DLBCL, particularly when used in combination with Acalabrutinib, positioning IRAK4-IN-15 as a valuable tool in cancer research.
IRAK4-IN-30 is a potent inhibitor of IRAK4, with an IC50 of 0.6 nM. This compound effectively modulates the signaling pathways associated with the innate immune response. It is valuable for research applications focused on inflammation, autoimmunity, and cancer, providing insights into the mechanistic roles of IRAK4 in various biological processes.
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IRAK4-IN-17 is a potent inhibitor of IRAK4, exhibiting an IC50 of 1.3 nM. This compound is instrumental for research involving diffuse large B-cell lymphoma (DLBCL), providing insight into the role of IRAK4 in oncogenic signaling pathways. Its high specificity and efficacy make it a valuable tool for investigating therapeutic strategies targeting IRAK4-related mechanisms in cancer biology.
ND-2158 is a competitive inhibitor of IRAK4, exhibiting a Ki value of 1.3 nM. This compound effectively suppresses LPS-induced TNF production in human white blood cells and demonstrates therapeutic potential by alleviating collagen-induced arthritis and preventing gout formation in mouse models. Additionally, ND-2158 shows antitumor activity in vivo, making it a valuable tool for research in inflammation and cancer biology.
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PROTAC IRAK4 Degrader-10 is a potent IRAK4 degrader that utilizes a Cereblon ligand to initiate targeted protein degradation. It demonstrates remarkable biological activity, achieving a maximum degradation of 95.94% with a DC50 value of 7.68 nM in HEK293 cells. This compound is essential for research applications focused on inflammatory signaling pathways and therapeutic strategies targeting IRAK4.
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PROTAC IRAK4 Degrader-6 is a Cereblon-based PROTAC designed to selectively degrade interleukin-1 receptor-associated kinase 4 (IRAK4). This compound targets IRAK4 for ubiquitination and subsequent proteasomal degradation, effectively modulating inflammatory signaling pathways. It is utilized in research applications focused on understanding the role of IRAK4 in immune responses and developing novel therapeutic strategies for inflammatory diseases.
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IRAK4-IN-11 is a selective inhibitor of interleukin-1 receptor-associated kinase 4 (IRAK4), demonstrating a potent inhibition profile with an IC50 of 0.008 µM. This compound effectively suppresses phosphorylated IRAK4 with an IC50 of 0.19 µM, making it a valuable tool for studying the IL-1 signaling pathway. IRAK4-IN-11 is suitable for research applications focused on inflammation, immune response, and related therapeutic areas.
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