il 4 inhibitor 1

IL-4 inhibitor is an inhibitor of IL-4.1It binds to IL-4 with a Kdvalue of 1.8 μM and inhibits IL-4 activity in a cell-based reporter assay (EC50= 1.81 μM). It is selective for IL-4 over IL-13 (EC50= 18.2 μM). IL-4 inhibitor inhibits IL-4-induced STAT6 phosphorylation in THP-1 monocytes (EC50= 3.1 μM), indicating inhibition of the IL-4-JAK1-STAT6 signaling pathway.

BI-69A11 ((E)-3-(1H-Benzo[d]imidazol-2-yl)-1-(6-chloro-2-hydroxy-4-phenylquinolin-3-yl)prop-2-en-1-one) is a dual AKT and NFkB pathway inhibitor. It enhances the susceptibility of colon cancer cells to mda-7/IL-24-induced growth inhibition by targeting Akt.

Through its effects on ULK1 and ULK2, MRT67307 blocks autophagy. MRT67307 prevents the phosphorylation of IRF3 and the production of IFN-β and increases toll-like receptor-induced IL-10 and IL-1ra secretion in macrophages. MRT67307 is a kinase inhibitor that has been shown to inhibit TBK1, MARK1-4, IKKε, and NUAK1 (IC50 values are 19, 27-52, 160, and 230 nM, respectively), the salt-inducible kinases (SIKs; IC50s =250, 67, and 430 nM for SIK1, SIK2, and SIK3, respectively) and ULK1 and ULK2 (IC50s = 45 and 38 nM, respectively).

IRAK4-IN-4 (compound 15) inhibits cyclic GMP-AMP synthase (cGAS) with an IC50 of 2.1 nM.IRAK4-IN-4 is an interleukin-1 receptor–associated kinase 4 (IRAK4) inhibitor, has an IC50 of 2.8 nM.

AZ1495 is an oral active inhibitor of Interleukin-1 receptor associated kinase 4 (IRAK4), with IC50 values of 5 nM and 23 nM for IRAK4 and IRAK1, respectively. Which Shows activity in treatment of mutant MYD88L265P diffuse large B-cell lymphoma (DLBCL).

PQA-18, an inhibitor of p21-activated kinase 2 (PAK2; IC50 = 10 nM), is derived from Ppc-1 and exhibits immunosuppressive properties. It inhibits IL-2 production in Jurkat T cells induced by Concanavalin A (product number 14951) with an IC50 of 400 nM. Topically applied at 0.1%, PQA-18 reduces the severity of atopic dermatitis, serum IgE levels, and skin thickness in the NC/Nga mouse model. A lower concentration of 0.05% also decreases skin nerve fiber density in NC/Nga mice. Additionally, PQA-18 administered at 4 mg/kg improves graft survival in a rat small intestine transplantation model.

JAK1/2-IN-1 is a potent inhibitor of JAK1 and JAK2, with IC50 values of 0.4 nM and 8.1 nM, respectively. Additionally, JAK1/2-IN-1 inhibits IL-4 and IL-13, with IC50 values of 136.5 nM and 19.1 nM, respectively (WO2023244775A1; Example 33a).

CD-10 is an orally active inhibitor of the Keap1-Nrf2 protein-protein interaction (PPI) that can penetrate the blood-brain barrier. It binds to Keap1 with a KD value of 193 nM. CD-10 exerts significant antioxidant and anti-inflammatory effects by activating the Keap1-Nrf2 pathway, demonstrated by reduced levels of MDA, IL-4, and IL-10, and increased expression of HO-1 protein. In a chronic unpredictable mild stress (CUMS) mouse model, CD-10 effectively alleviates anxiety and depressive behaviors and restores serum neurotransmitter levels by promoting Nrf2 nuclear translocation. CD-10 is applicable for research in depression.

ADAM17-IN-1 is a selective ADAM17 inhibitor. It functions by reducing dendritic cell (DC) metabolic activity through ADAM17 inhibition, thereby impairing DC antigen presentation, suppressing allergen-specific Th2 cell polarization, and decreasing the secretion of Th2 cytokines (IL-4, IL-5, IL-13). In mouse models of house dust mite (HDM)-induced type 2/eosinophilic airway inflammation, ADAM17-IN-1 demonstrates protective effects. This compound can be utilized in research on type 2 hyperreactive allergic asthma.

IRAK-1-4 Inhibitor I is a dual inhibitor targeting IRAK1 and IRAK4.

Clerodendrin (Apigenin-7-O-glucuronopyranosyl(1-2)-glucuronopyranoside) is a new neodentate diterpenoid isolated from the leaves of Clerodendron trichotomm, a radish sawfly Athalia Clerodendrin is an interleukin-4 (IL-4) inhibitor and β-hexosaminidase (Hex) inhibitor.

CC-90005 is a potent, selective, and orally active inhibitor of protein kinase C-θ (PKC-θ) with an IC50 of 8 nM, demonstrating strong selectivity over PKC-δ (IC50=4440 nM). Additionally, CC-90005 can inhibit T cell activation by IL-2 expression[1].

T-5342126 is a toll-like receptor 4 (TLR4) antagonist that reduces LPS-induced production of nitric oxide (NO) in RAW 264.7 cells (IC50 = 27.8 μM) and decreases LPS-induced IL-8, TNF-α, and IL-6 production in isolated human whole blood (IC50s = 110.5, 315.6, and 318.4 μM, respectively). T-5342126 (82 mg/kg) also reduces ethanol intake and the abundance of ionized calcium-binding adapter molecule 1 (Iba1), a marker of microglial activation, in the central nucleus of the amygdala in ethanol-dependent mice.

Givinostat (ITF-2357) is an HDAC inhibitor with IC50 values of 198 nM for HDAC1 and 157 nM for HDAC3.

p38 MAPK inhibitor (IC50 = 0.38 μM). Inhibits the release of IL-1β and TNF-α in a peripheral blood mononuclear cell (PBMC) assay (IC50 values are 0.039 and 0.16 μM respectively). Laufer et al (2003) Novel substituted pyridinyl imidazoles as potent anticytokine agents with low activity against hepatic cytochrome P450 enzymes. J.Med.Chem. 46 3230 PMID:12852754 |Kammerer et al (2007) Pharmacokinetics of ML3403 ({4-[5-(4-fluorophenyl)-2-methylsulfanyl-3H-imidazol-4-yl]-pyridin-2-yl}-(1-phenylethyl)-amine), a 4-pyridinylimidazole-type p38 mitogen-activated protein kinase inhibitor. Drug Metab.Dispos. 35 875 PMID:17344341

Interleukin-2-inducible T cell kinase (ITK) is a non-receptor tyrosine kinase expressed in T cells, NKT cells and mast cells which plays a crucial role in regulating the T cell receptor (TCR), CD28, CD2, chemokine receptor CXCR4, and FcepsilonR-mediated signaling pathways. ITK inhibitors can be used for the treatment of inflammation and immune-mediated disorders. ITK inhibitor (N-[5-[[3-[(4-Acetylpiperazin-1-yl)carbonyl]-4-methyl-6-methoxy-phenyl]thio]thiazol-2-yl]-4-(N-1,2-dimethylpropylaminomethyl)benzamide) is the analogue of BMS-509744, which can potently and selectively inhibit Itk kinase activity. In vitro: BMS-509744 could reduce TCR-induced functions including PLCγ1 tyrosine phosphorylation, calcium mobilization, IL-2 secretion, and T-cell proliferation in vitro in both human and mouse cells [1]. In vivo: BMS-509744 suppressed the production of IL-2 induced by anti-TCR antibody administered to mice. BMS-509744 also significantly diminishes lung inflammation in a mouse model of ovalbumin-induced allergy/asthma [1]. Clinical trial: Up to now, both BMS-509744 and ITK inhibitor is still in the preclinical development stage.

LDN 0088050 is selectivity adipocyte fatty acid binding protein (AFABP, FABP4) inhibitor with Ki values of 0.29 and 1.3 μM for FABP4 and FABP3, respectively. LDN 0088050 binds to FABP4 with a Kd of 2.05 μM[1]. Ki: 0.29 μM (FABP4), 1.3 μM (FABP3)[1]Kd: 2.05 μM (FABP4)[1] LDN 0088050 significantly inhibits LPS-induced expression of both TNFα and IL-6 in RAW264.7 cells[1]. [1]. Zhou Y, et al. The discovery of novel and selective fatty acid binding protein 4 inhibitors by virtual screening and biological evaluation. Bioorg Med Chem. 2016 Sep 15;24(18):4310-4317.

JC-171, a selective inhibitor of the NLRP3 inflammasome, effectively inhibits LPS/ATP-induced interleukin-1β (IL-1β) release from J774A.1 macrophages with an IC50 of 8.45 μM[1].

IRAK4-IN-1 is an interleukin-1 receptor-associated kinase 4 (IRAK4) inhibitor with an IC50 of 7 nM.

AS-2444697 is an inhibitor of IRAK-4 (C50 = 21 nM). AS-2444697 exhibits renoprotective effects through anti-inflammatory action. AS-2444697 potently inhibits human and rat IRAK-4 activity.

IRAK inhibitor 1 is an effective IRAK-4 inhibitor (IC50: 216 nM), is poorly active against JNK-1 (IC50: 3.801 μM) and JNK-2 (IC50>10 μM).

IRAK inhibitor 6 is an inhibitor of interleukin-1 receptor-associated kinase 4 [IRAK-4, IC50: 160 nM].

IRAK4-IN-7 (CA-4948) is a selective and potent IRAK4 kinase inhibitor with in vivo activity in a TLR4-induced cytokine release model.

HS-243 is an inhibitor of IRAK-4 and IRAK-1 with IC50s of 20 and 24 nM. HS-243 shows anti-inflammatory and anticancer activity.