IRAK

IRAK1/4/pan-FLT3 Kinase-IN-2 is a dual inhibitor targeting IRAK1, IRAK4, and FLT3 with IC50 values of 10 nM, 0.7 nM, and <0.5 nM, respectively. This compound demonstrates significant biological activity by extending survival in acute myeloid leukemia model mice. It serves as a valuable tool for research in hematological malignancies and associated therapeutic pathways, facilitating studies on the modulation of kinase activity in cancer.

IRAK4-IN-16 is a potent inhibitor of interleukin-1 receptor associated kinase 4 (IRAK4), displaying an IC50 value of 2.5 nM. This compound demonstrates significant cytotoxic effects against various lymphoma cell lines, including OCI-LY10, TMD8, Ramos, and HT, with respective IC50 values of 0.2 μM, 0.2 μM, 0.6 μM, and 2.7 μM. IRAK4-IN-16 is valuable for research in the mechanisms of inflammation and cancer therapy, particularly in targeting IRAK4-related pathways.

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.

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.

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).

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.

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.

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.

IRAK4-IN-19 is a potent inhibitor of interleukin-1 receptor-associated kinase 4 (IRAK4), with an IC50 value of 4.3 nM. This compound effectively inhibits lipopolysaccharide (LPS)-induced IL-23 production in THP-1 and dendritic cells, demonstrating its ability to influence inflammatory pathways. IRAK4-IN-19 is valuable for research focused on arthritis and other inflammatory diseases, as it has shown efficacy in preventing the development of arthritis in animal models.

HG-12-6 is a type II inhibitor of IRAK4, exhibiting preferential binding to unphosphorylated inactive IRAK4 with an IC50 of 165 nM. This compound effectively modulates IRAK4 activity, making it a valuable tool for studying its role in autoimmunity and inflammation. Researchers can utilize HG-12-6 to investigate pathways associated with immune responses and inflammatory disorders.

IRAK4-IN-25 is a potent inhibitor of IRAK4, with an IC50 of 7.3 nM, demonstrating significant oral bioavailability and low clearance (Cl=12 mL/min/kg). This compound effectively inhibits the production of pro-inflammatory cytokines, making it a valuable tool for studying inflammatory and autoimmune disorders. Its in vitro safety and ADME profiles further support its potential applications in research aimed at understanding immune response modulation.

IRAK4-IN-24 is a potent inhibitor of IRAK4, a key kinase involved in the signaling pathways of inflammatory responses. This compound demonstrates significant biological activity, particularly in models of inflammatory and autoimmune disorders. IRAK4-IN-24 facilitates research into the modulation of immune responses and provides insights into potential therapeutic strategies targeting IRAK4 in various disease contexts.

IRAK4-IN-26 is a potent inhibitor of IRAK4 with an IC50 of 6.2 nM. This compound exhibits an oral bioavailability of 21%, making it suitable for in vivo studies. IRAK4-IN-26 is valuable for research into inflammatory and autoimmune disorders, facilitating the exploration of therapeutic strategies targeting IRAK4 signaling pathways.

BMS-978299 is a selective inhibitor of IRAK4, a critical kinase in the Toll-like receptor (TLR) signaling pathway. This compound demonstrates potent activity in modulating immune response and inflammation, making it a valuable tool for investigating immune disorders and related therapeutic interventions. Researchers can utilize BMS-978299 to further understand the role of IRAK4 in various pathophysiological conditions and to explore potential treatment strategies for immune-related diseases.

IRAK4-IN-34 is a potent and selective inhibitor of Interleukin-1 receptor-associated kinase 4 (IRAK4), exhibiting an IC50 of 0.73 nM. This compound demonstrates significant selectivity against hERG and other kinase targets. With favorable pharmacokinetic properties for in vivo applications, IRAK4-IN-34 is valuable for research into inflammatory diseases and related pathways.

ND-2110 is a selective inhibitor of IRAK4, exhibiting a binding affinity with a Ki of 7.5 nM. It effectively targets the ATP binding site of IRAK4 and demonstrates significant biological activity in activated B cell-like (ABC) subtype diffuse large B cell lymphoma (DLBCL) cell lines harboring MYD88 L265P mutations. ND-2110 has been shown to inhibit LPS-induced TNF production and demonstrates therapeutic potential in mouse models of collagen-induced arthritis and gout.

HPK1-IN-7 is a potent inhibitor of hematopoietic progenitor kinase 1 (HPK1, MAP4K1) with an IC50 of 2.6 nM, demonstrating excellent selectivity among kinases. It exhibits some selectivity against IRAK4 and GLK, with IC50 values of 59 nM and 140 nM, respectively. This compound has shown significant efficacy in the MC38 syngeneic tumor model, particularly when used in combination with anti-PD1 therapy, highlighting its potential in immuno-oncology research.