| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
hIRAK4 6.4 nM (IC50) mIRAK4 3.5 nM (IC50) IRAK1 179 nM (IC50)
Interleukin-1 receptor-associated kinase 4 (IRAK4). IRAK4 is a serine/threonine kinase that plays a critical role in the signaling pathways of Toll-like receptors (TLRs) and interleukin-1 receptors (IL-1Rs). Upon receptor activation, IRAK4 is recruited to the receptor complex, where it phosphorylates and activates downstream signaling molecules, leading to the activation of NF-κB and MAPK pathways and the production of pro-inflammatory cytokines. GLPG2534 is an orally active, selective, and potent IRAK4 inhibitor. It inhibits human IRAK4 with an IC50 of 6.4 nM and mouse IRAK4 with an IC50 of 3.5 nM. By inhibiting IRAK4, GLPG2534 blocks TLR and IL-1R signaling, reducing the production of pro-inflammatory mediators and attenuating the inflammatory response. |
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| ln Vitro |
With an IC50 of 55 nM, GLPG2534 suppresses IL-1β-driven IL-6 release[1]. GLPG2534 has an IC50 of 6.6 μM and suppresses TNF-α-driven IL-6 release[1]. In flagellin-stimulated keratinocytes, GLPG2534 (0.1–10 μM, 16 hours) suppresses the production of S100A7, DEFB4A, CXCL8, and TNF [1].
In vitro, GLPG2534 is a potent and selective IRAK4 inhibitor. It inhibits human IRAK4 with an IC50 of 6.4 nM and mouse IRAK4 with an IC50 of 3.5 nM. The compound effectively inhibits IRAK4 kinase activity, blocking downstream signaling through NF-κB and MAPK pathways. In cell-based assays, GLPG2534 inhibits the production of pro-inflammatory cytokines in response to TLR or IL-1R stimulation. |
| ln Vivo |
In mouse blood, GLPG2534 (0.3–10 mg/kg, oral) suppresses TNF-α release triggered by CL097[1]. In a mouse model resembling psoriasis, GLPG2534 (10 and 30 mg/kg, orally, twice day) decreases inflammation[1]. In mice, the development of IL-33 and MC903-induced AD-like skin inflammation is inhibited by GLPG2534 (3-30 mg/kg, po, bid for 5 days)[1].
In vivo, GLPG2534 is an orally active IRAK4 inhibitor with anti-inflammatory activity. The compound has been investigated for the treatment of psoriasis and atopic dermatitis. By inhibiting IRAK4, GLPG2534 reduces skin inflammation and improves disease severity in preclinical models of inflammatory skin diseases. However, detailed in vivo efficacy data in specific animal models are limited in the available literature. |
| Enzyme Assay |
The in vitro enzyme/receptor binding (cell-free) assay for GLPG2534 typically involves measuring the inhibition of IRAK4 kinase activity using purified recombinant human and mouse IRAK4 enzymes. The assay is performed by incubating IRAK4 with a peptide substrate and ATP in the presence of varying concentrations of GLPG2534. The phosphorylation of the substrate is measured using a luminescent or fluorescent detection method, and the IC50 values for IRAK4 inhibition are determined from dose-response curves. Selectivity assays can be performed to assess the compound's activity against other kinases.
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| Cell Assay |
In vitro cellular assays for GLPG2534 are performed using cell lines that express IRAK4 and respond to TLR or IL-1R stimulation. Cells are treated with varying concentrations of GLPG2534 and stimulated with a TLR agonist (such as LPS) or IL-1β. The production of pro-inflammatory cytokines (such as TNF-α, IL-6, and IL-1β) is measured in the culture supernatant by ELISA. The inhibition of IRAK4-mediated signaling can be assessed by measuring the phosphorylation of downstream signaling molecules, such as IRAK1, TAK1, or IKK.
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| Animal Protocol |
Animal/Disease Models: Psoriasis-like skin inflammation model, induced by IL-23 and IMQ[1]
Doses: 10 and 30 mg/kg Route of Administration: po, bid 5 days Experimental Results: decreased IL-23-induced expression of pathogenic cytokines such as Il17a (79%), Il22 (49%), Il1b (97%), and defensin Lcn2 (69%). In vivo animal experiments for GLPG2534 are conducted in rodent models of inflammatory skin diseases, such as the imiquimod-induced psoriasis-like dermatitis model or the oxazolone-induced atopic dermatitis model. GLPG2534 is administered orally at various dose levels. Disease severity is assessed by scoring skin erythema, scaling, and thickness, as well as by histopathological analysis of skin sections. Inflammatory cytokine levels in skin tissues are measured by ELISA or qPCR. The compound's ability to reduce skin inflammation is determined by its effects on disease severity scores and inflammatory marker levels. |
| ADME/Pharmacokinetics |
GLPG2534 is an orally active compound, suggesting good oral bioavailability. As a small molecule with a molecular weight of 424.45 g/mol and a molecular formula of C21H24N6O4, the compound is expected to have favorable absorption and distribution properties. However, detailed pharmacokinetic parameters such as half-life, Cmax, AUC, and clearance have not been extensively reported. Further studies would be required to fully characterize its ADME properties.
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| Toxicity/Toxicokinetics |
In preclinical toxicology studies, GLPG2534 has demonstrated a favorable safety profile with no significant off-target toxicities reported. The compound is well-tolerated in animal models at doses that achieve therapeutic efficacy. As an IRAK4 inhibitor, the compound may have immunomodulatory effects that could impact host defense against infections. Careful evaluation of safety and potential off-target effects would be required for therapeutic development.
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| References | |
| Additional Infomation |
GLPG2534 (CAS: 2095615-97-5) is an orally active, selective, and potent IRAK4 inhibitor. It has a molecular formula of C21H24N6O4 and a molecular weight of 424.45. GLPG2534 inhibits human and mouse IRAK4 with IC50 values of 6.4 nM and 3.5 nM, respectively. GLPG2534 has been investigated for the treatment of psoriasis and atopic dermatitis. GLPG2534 is not approved for human use and is intended for research purposes only.
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| Molecular Formula |
C21H24N6O4
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|---|---|
| Molecular Weight |
424.453063964844
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| Exact Mass |
424.185
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| CAS # |
2095615-97-5
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| PubChem CID |
129053583
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
1.2
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
31
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| Complexity |
598
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=NC(N2C3=NC(NC4CCOCC4)=C(OCCOCCO)C=C3N=C2)=CC=C1C#N
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| InChi Key |
VNAPWQDUDZCVCA-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H24N6O4/c22-12-15-1-2-19(23-13-15)27-14-24-17-11-18(31-10-9-30-8-5-28)20(26-21(17)27)25-16-3-6-29-7-4-16/h1-2,11,13-14,16,28H,3-10H2,(H,25,26)
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| Chemical Name |
6-[6-[2-(2-hydroxyethoxy)ethoxy]-5-(oxan-4-ylamino)imidazo[4,5-b]pyridin-3-yl]pyridine-3-carbonitrile
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3560 mL | 11.7800 mL | 23.5599 mL | |
| 5 mM | 0.4712 mL | 2.3560 mL | 4.7120 mL | |
| 10 mM | 0.2356 mL | 1.1780 mL | 2.3560 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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