IRAK4 Inhibitor

KT-474 (KYM-001; PROTAC IRAK4 degrader-7) is an orally active PROTAC IRAK4 degrader with anti-tumor effects. KT-474 inhibits the cell cycle and induces apoptosis. KT-474 induces tumor regression in a xenograft model of MYD88-mutated ABC DLBCL.

Zimlovisertib (PF-06650833) is a potent, selective and orally active inhibitor of interleukin-1 receptor associated kinase 4 (IRAK4) with IC₅₀s of 0.2 and 2.4 nM in the cell and PBMC assay, respectively. Zimlovisertib is used to treat diseases such as rheumatoid arthritis, lupus, and lymphomas.

AS2444697 is an orally active IRAK-4 inhibitor with an IC₅₀ of 21 nM. AS2444697 potently inhibits human and rat IRAK-4 activity. AS2444697 exhibits renoprotective effects through anti-inflammatory action.

Emavusertib is an orally active inhibitor for IRAK4 (IC₅₀=57 nM) and FLT3. Emavusertib inhibits NF-κB and MyD88 signaling pathways, reduces the generation of pro-inflammatory cytokines like IL-6 and IL-10, thereby exhibiting anti-inflammatory and anti-proliferative activities against cancer cells, leading to cell apoptosis. Emavusertib exhibits antitumor activity in mouse model

Zabedosertib (BAY 1834845) is a selective, orally active IRAK4 inhibitor with immunomodulatory potential, IC₅₀ is 3.55 nM. IRAK4 is a protein kinase involved in signaling innate immune responses from Toll-like receptors. Zabedosertib exhibits anti-inflammatory property against IL-β, LPS (HY-D1056) and Imiquimod (HY-B1080) induced inflammation.

IRAK1/4/pan-FLT3 Kinase-IN-1 hydrochloride is an orally active, potent and selective IRAK/pan-FLT3 kinase inhibitor with IC₅₀s of 5 nM, 0.6 nM and <0.5 nM against IRAK1, IRAK4 and FLT3, respectively. IRAK1/4/pan-FLT3 Kinase-IN-1 hydrochloride can be used for research on AML.

HS-276 is an orally active, potent and highly selective TAK1 inhibitor, with a K_i of 2.5 nM. HS-276 shows significant inhibition of TAK1, CLK2, GCK, ULK2, MAP4K5, IRAK1, NUAK, CSNK1G2, CAMKKβ-1, and MLK1, with IC₅₀ values of 8.25, 29, 33, 63, 125, 264, 270, 810, 1280, and 5585 nM, respectively. HS-276 reduces the expression of TNF, IL-6, and IL-1β. HS-276 can be used for rheumatoid arthritis (RA) research.

KME-2780 is the orally active inhibitor for IRAK1 and IRAK4 with IC₅₀s of 19 nM and 0.5 nM. KME-2780 can be used for research of dysregulation of innate immune signaling and hematologic malignancies.

AZ1495, a weak base, is a potent orally active interleukin-1 receptor associated kinase 4 (IRAK4) inhibitor. AZ1495 has a favorable physicochemical and kinase selectivity for IRAK4 and IRAK1 with IC₅₀ values of 0.005 μM and 0.023 μM, respectively. AZ1495 has IRAK4 inhibition with a K_d value of 0.0007 μM. AZ1495 can be used for the research of diffuse large B-cell lymphoma (DLBCL).

IRAK4-IN-4 (Compound 15) is an interleukin-1 receptor-associated kinase 4 (IRAK4) inhibitor, with an IC₅₀ of 2.8 nM. IRAK4-IN-4 also inhibits cyclic GMP-AMP synthase (cGAS) with an IC₅₀ of 2.1 nM. IRAK4-IN-4 can be used for research of autoimmune diseases.

BIO-7488 is an orally active, selective and blood-brain barrier permeable IRAK4 inhibitor, with an IC₅₀ value of 0.5 nM. BIO-7488 inhibits the production of pro-inflammatory cytokines (IL-1β, TNFα, IL-6) and demonstrates anti-inflammatory effects in both LPS (HY-D1056) and distal hypoxic-middle cerebral artery occlusion (DH-MCAO) ischemic stroke model. BIO-7488 can be used for the study of neuroinflammatory-related diseases, particularly ischemic stroke.

HS-243 is a potent and selective IRAK-4 and IRAK-1 inhibitor, with IC₅₀ values of 20 and 24 nM. HS-243 shows minimal TAK1 (transforming growth factor β-activated kinase 1) inhibition activity, with a IC₅₀ of 0.5 μM. HS-243 shows anti-inflammatory and anticancer activity.

IRAK1/4/pan-FLT3 Kinase-IN-1 is an orally active, potent and selective IRAK/pan-FLT3 kinase inhibitor with IC₅₀s of 5 nM, 0.6 nM and <0.5 nM against IRAK1, IRAK4 and FLT3, respectively. IRAK1/4/pan-FLT3 Kinase-IN-1 can be used for research on AML.

IRAK4-IN-7 is a selective, potent and orally active interleukin-1 receptor-associated kinase 4 (IRAK4) inhibitor, extracted from patent WO2015104688 (example 1). IRAK4-IN-7 has the potential for cancer and inflammatory diseases treatment.

IRAK4-IN-20 (Compound BAY-1834845) is an orally active IRAK4 inhibitor with an IC₅₀ of 3.55 nM. IRAK4-IN-20 can be used for acute respiratory distress syndrome (ARDS) research.

GLPG2534 is an orally active and selective IRAK4 inhibitor, with IC₅₀ values of 6.4 nM and 3.5 nM for human and mouse IRAK4. GLPG2534 can be used for the research of inflammatory skin diseases.

IRAK-4 protein kinase inhibitor 2 (compound 1) is a potent inhibitor of interleukin-1 (IL-1) receptor-associated kinase-4 (IRAK-4), with an IC₅₀ of 4 μM. IRAK-4 protein kinase inhibitor 2 can be used for the research of inflammatory and immune-related conditions or disorders.

IRAK4-IN-14 (compound 28) is a potent, selective and orally active IRAK4 inhibitor with an IC₅₀ of 0.003 µM. IRAK4-IN-14 shows good PK parameters in rats and mouse. IRAK4-IN-14 shows synergistic in vitro activity against MyD88/CD79 double mutant ABC-DLBCL in combination with Acalabrutinib.

PF-06426779 is a potent and selective inhibitor of interleukin 1 receptor associated kinase 4 (IRAK4), with an IC₅₀ of 0.3 nM.

IRAK inhibitor 2 is an interleukin-1 receptor-associated kinase (IRAK) inhibitor. IRAK inhibitor 2 can be used for the research of inflammatory and immune diseases.