| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
|
||
| 25mg | |||
| 50mg | |||
| 100mg | |||
| Other Sizes |
| Targets |
MAPK-activated protein kinase 5 (MK5/MAPKAPK5). GLPG0259 is an ATP-competitive inhibitor. It interacts with the ATP-binding site of the MAPKAPK5 enzyme, thereby inhibiting its activity.
|
|---|---|
| ln Vitro |
GLPG0259 inhibits the phosphorylation of p38 MAP, ERK, and c-jun NH(2)-cutin inhibitor (JNK), however it has no effect on the release of regulatory and bone degradation mediators [1]. In the shrimp cancer (PCa) cell lines LNCaP and PC3, GLPG0259 (1–5 μM; 48 h) reduces actin filaments and results in cell death [2].
GLPG0259 is an ATP-competitive inhibitor of MAPKAPK5. It plays a role in modulating biochemical reactions involved in inflammation and bone degradation. MAPKAPK5 is a key regulator of cytokine production, making it a potential target for rheumatoid arthritis (RA) treatment. |
| ln Vivo |
In SCID beige tumors with P3 cell line (iv), GLPG0259 (2 mg/kg, 10 mg/kg; intraperitoneal injection; twice weekly for 7 weeks) prevents tumor cell spread in the lungs [2].
GLPG0259 reduces inflammation and bone destruction in a mouse collagen-induced arthritis model. It has oral activity. As an inhibitor of MAPKAPK5, a kinase that plays a role in inflammatory pathways, it has been investigated for the treatment of rheumatoid arthritis. |
| Enzyme Assay |
MAPKAPK5 kinase activity assays are performed using recombinant human MAPKAPK5 enzyme and a peptide substrate. The enzyme is incubated with the substrate and [γ-32P]ATP or fluorescently labeled ATP in kinase buffer (50 mM HEPES pH 7.5, 10 mM MgCl2, 1 mM DTT). The reaction is incubated at 30°C for 30-60 minutes. Phosphorylated substrate is quantified by scintillation counting or fluorescence polarization. GLPG0259 is serially diluted and added to the reaction mixture. IC50 values are determined by non-linear regression analysis. Each concentration is tested in duplicate.
|
| Cell Assay |
Cellular MAPKAPK5 inhibition is evaluated in immune cells or cell lines. Cells are cultured in appropriate media at 37°C with 5% CO2 and treated with GLPG0259 at various concentrations. MAPKAPK5 activity in cell lysates is measured using kinase assays. Cytokine production (e.g., TNF-α, IL-6) is measured by ELISA. Cell viability is assessed using MTT or LDH assays. Each experiment includes known kinase inhibitors as positive controls and vehicle controls.
|
| Animal Protocol |
In vivo efficacy is evaluated in the mouse collagen-induced arthritis model. DBA/1 mice are immunized with bovine type II collagen in Freund's complete adjuvant. GLPG0259 is administered orally at doses determined by preclinical studies. Clinical arthritis scores are assessed based on paw swelling and redness. Paw thickness is measured using calipers. At study endpoint, joints are collected for histopathological analysis (H&E staining, Safranin O staining). Serum levels of inflammatory cytokines are measured by ELISA. Blood samples are collected for pharmacokinetic analysis. Sample sizes typically range from 8-10 animals per group.
|
| ADME/Pharmacokinetics |
Molecular Weight: 460.53. Formula: C24H28N8O2. CAS No.: 959754-85-9. Purity: ≥99.0%. Appearance: Solid. Solubility: DMSO 3 mg/mL. Storage: Powder -20°C. Shipping: Ice bag.
|
| Toxicity/Toxicokinetics |
No comprehensive toxicology data are publicly available. As a MAPKAPK5 inhibitor, potential toxicities may include effects on inflammatory pathways and immune function. Standard toxicity studies would include acute and subchronic toxicity in rodents, genotoxicity screening, and evaluation of effects on the immune system. No clinical trials have been reported for this compound. The compound is intended for research use only.
|
| References |
|
| Additional Infomation |
GLPG0259 is also known as GLPG-0259. It is an ATP-competitive inhibitor of MAPKAPK5 with oral activity. It reduces inflammation and bone destruction in a mouse collagen-induced arthritis model. No clinical trials or regulatory approvals have been reported. The compound is for research use only.
|
| Molecular Formula |
C24H28N8O2
|
|---|---|
| Molecular Weight |
460.53152
|
| Exact Mass |
460.234
|
| CAS # |
959754-85-9
|
| Related CAS # |
1195065-29-2 ;959754-85-9;
|
| PubChem CID |
57589985
|
| Appearance |
Off-white to yellow solid powder
|
| LogP |
3.923
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
8
|
| Rotatable Bond Count |
6
|
| Heavy Atom Count |
34
|
| Complexity |
702
|
| Defined Atom Stereocenter Count |
0
|
| InChi Key |
DLGZLIXYVSQGOX-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C24H28N8O2/c1-24(2,3)31-10-8-30(9-11-31)18-6-4-17(5-7-18)29-22-23-27-15-28-32(23)19(13-26-22)16-12-20(21(25)33)34-14-16/h4-7,12-15H,8-11H2,1-3H3,(H2,25,33)(H,26,29)
|
| Chemical Name |
4-[8-[4-(4-tert-butylpiperazin-1-yl)anilino]-[1,2,4]triazolo[1,5-a]pyrazin-5-yl]furan-2-carboxamide
|
| Synonyms |
GLPG-0259 GTPL9848GLPG 0259 GTPL-9848GLPG0259 GTPL 9848
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~3.33 mg/mL (~7.23 mM)
|
|---|---|
| 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 | 2.1714 mL | 10.8571 mL | 21.7141 mL | |
| 5 mM | 0.4343 mL | 2.1714 mL | 4.3428 mL | |
| 10 mM | 0.2171 mL | 1.0857 mL | 2.1714 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
