ND2158 (ND-2158) is a highly potent and selective IRAK4 inhibitor with IC50 of 1.3 nM;ND2158 demonstrates high selectivity against 334 kinases, and >1000-fold over IRAK1.ND2158 blocked TNF production, collagen-induced arthritis, and gout formation in mice, suppressed LPS-induced TNF production, alleviated collagen-induced arthritis, and blocked gout formation in mouse models.IRAK4 inhibition promoted killing of ABC DLBCL lines harboring MYD88 L265P, by down-modulating survival signals, including NF-κB and autocrine IL-6/IL-10 engagement of the JAK-STAT3 pathway.In ABC DLBCL xenograft models, IRAK4 inhibition suppressed tumor growth as a single agent, and in combination with the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib or the Bcl-2 inhibitor ABT-199.
A potent, selective, orally bioavailable IRAK-4 inhibitor that potently inhibits human and rat IRAK-4 activity with subnanomolar order, >30-fold selectivity over IRAK-1; inhibited IL-1β- or TLR ligand lipopolysaccharide (LPS)-induced IL-6 production in human lung alveolar epithelial cells, fibroblast-like synoviocytes, and peripheral blood mononuclear cells; significantly reduces urinary protein excretion and preventd the development of glomerulosclerosis and interstitial fibrosis without affecting the blood pressure in mice model of chronic kidney disease.
Larotinib mesylate hydrate is a potent broad-spectrum and orally active tyrosine kinase inhibitor (TKI) with EGFR as the main target with an IC50 of 0.6 nM[1].
Ginsenoside Rb1, a main constituent of the root of Panax ginseng, inhibits Na+, K+-ATPase activity with an IC50 of 6.3±1.0 μM. Ginsenoside also inhibits IRAK-1 activation and phosphorylation of NF-κB p65 .
Emavusertib (CA-4948) hydrochloride is a selective, potent and orally active IRAK4/FLT3 inhibitor. Emavusertib hydrochloride has an IC50 of 57 nM for IRAK4 in a FRET kinase assay. Emavusertib hydrochloride shows anti-tumor activity[1][2][3].
IRAK4-IN-21 (compound 17) is an orally active, potent and selective IRAK4 inhibitor with IC50 values of 5 and 56 nM for IRAK4 and TAK1, respectively. IRAK4-IN-21 effectively inhibits IL-23 production (IC50=0.17 µM) and can be used in studies of autoimmune diseases such as plaque psoriasis and psoriatic arthritis[1].
PROTAC IRAK4 degrader-8 (compound 2) is a PROTAC targeting to IRAK4 (IC50=15.5 nM)[1].
IRAK4-IN-22 (compound 18) is an orally active, potent and selective IRAK4 inhibitor with IC50 values of 3 and 17 nM for IRAK4 and TAK1, respectively. IRAK4-IN-21 effectively inhibits IL-23 production (IC50=0.10 µM) and can be used in studies of autoimmune diseases such as plaque psoriasis and psoriatic arthritis[1].
PROTAC IRAK4 degrader-5 is a PROTAC-based IRAK4 degrader extracted from patent US20190192668A1, compound I-171[1].
IRAK inhibitor 1 is a potent IRAK-4 inhibitor with IC50 of 216 nM, is poorly active against JNK-1 and JNK-2 with IC50 of 3.801 μM, and >10 μM, respectively.
IRAK-1-4 Inhibitor I is an inhibitor of interleukin-1 receptor-associated kinase 1/4 (IRAK 1/4) with IC50s of 0.2 μM and 0.3 μM, respectively.
PROTAC IRAK4 degrader-1 is a PROTAC interleukin-1 receptor-associated kinase 4 (IRAK4) degrader extracted from patent US20190192668A1 Compound I-210, makes <20%, >20-50%, and >50% IRAK4 degradation at 0.01, 0.1, and 1 μM in OCI-LY-10 cells, respectively[1].
HG-12-6 is a small-molecule inhibitor that bind preferentially to unphosphorylated IRAK4 with IC50 of 165.1 nM, displays 15-fold selectivity over phosphorylated IRAK4 (IC50=2876 nM); binds as type II inhibitor with IRAK4 in a “DFG-out” conformation.
HS-243 (HS243) is a highly potent, super-selective IRAK-1/4 inhibitor with IC50 of 24/20 nM, respectively.HS-243 shows exquisite potency toward IRAK-1/4 over all other human kinases with only minimal TAK1-inhibiting activity (IC50=0.5 uM).HS-243 binds in the ATP-binding pocket of IRAK-4.HS-243 potently reduces the proinflammatory response of RA cells and macrophages, has distinct cytokine profile from TAK1.HS-243 reduces percentage of survival in pancreatic and breast cancer cell lines.
IRAK inhibitor 3 is an interleukin-1 (IL-I) receptor-associated kinase (IRAK) kinase modulator extracted from patent WO2008030579 A2.
IRAK inhibitor 6 is an inhibitor of interleukin-1 receptor associated kinase 4 (IRAK-4) with IC50 of 160 nM.
PROTAC IRAK4 degrader-7 (Compound I-417) is an orally active PROTAC IRAK4 degrader with antitumor activities[1].
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[1].
GNE-2256 (GNE2256) is a potent, selective inhibitor of IRAK4 with biochemical Ki of 1.4 nM.GNE-2256 displays high selectivity in the CEREP panel with off-targets with >50% inhibition are TACR1, HTR2B and ACHE.GNE-2256 is potent in the NanoBRET assay (IC50 = 3.3 nM), the IL-6 human whole blood assay (IC50=190 nM) and the IFNα human whole blood assay (IC50=290 nM).
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[1].
IRAK4-IN-17 (Compound 5) is a potent IRAK4 inhibitor with the IC50 of 1.3 nM[1]. IRAK4-IN-17 can be used in large B-cell lymphoma (DLBCL) research[1].
PROTAC IRAK4 degrader-4 is a PROTAC interleukin-1 receptor-associated kinase 4 (IRAK4) degrader extracted from patent US20190192668A1, compound I-127[1].
IRAK4-IN-16 (compound 4) is a potent IRAK4 (interleukin-1 receptor associated kinase 4) inhibitor, with an IC50 of 2.5 nM. IRAK4-IN-16 shows cytotoxicity activity against OCI-LY10, TMD8, Ramos and HT cells, with IC50 values of 0.2, 0.2, 0.6, and 2.7 μM, respectively[1].
IRAK inhibitor 4 is an interleukin-1 receptor associated kinase 4(IRAK4) inhibitor.
KTX-951 is an IRAK4 degrader (DC50=18 nM). KTX-951 (10 mg/kg) shows the oral bioavailability (F%) of 22% in a rat model. KTX-951 has good anticancer potential[1].
KTX-497 is an orally active IRAK4 degrader with a DC50 value of 3 nM. KTX-497 can be used for the research of oncology[1].
Zabedosertib (BAY 1834845) is a IRAK4 inhibitor with immunomodulatory potential. IRAK4 is a protein kinase involved in signaling innate immune responses from Toll-like receptors[1].
KTX-955 is a potent IRAK4 degrader with DC50 values of 5 nM and 130 nM for IRAK4 and Ikaros, respectively. KTX-955 can be used to research anticancer[1][2].
CA-4948 is a selective and potent IRAK4 inhibitor.
IRAK4-IN-4 is an interleukin-1 receptor–associated kinase 4 (IRAK4) inhibitor extracted from patent CN107163044A, Compound15, has an IC50 of 2.8 nM. IRAK4-IN-4 also inhibits cyclic GMP-AMP synthase (cGAS) with an IC50 of 2.1 nM[1].