| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| Other Sizes |
| Targets |
MK2 (MAPKAP-K2) (IC50 = 8.5 nM)
Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 (MK-2) (Ki = 1.8 nM; IC50 for MK-2 kinase activity = 3.2 nM) [1] |
|---|---|
| ln Vitro |
MK2-IN-3 (compound 16) suppresses MK-2 and TNFα production in U937 cells, with IC50 values of 4.4 μM and 8.5 nM, respectively [1].
MK2 Inhibitor III inhibited recombinant human MK-2 kinase activity in a dose-dependent manner, with Ki = 1.8 nM (measured by SPR) and IC50 = 3.2 nM (radiometric kinase assay) [1] - The compound showed high selectivity for MK-2: no significant inhibition of other related kinases (p38α, ERK1, JNK2, Akt1) at concentrations up to 10 μM (IC50 > 10 μM for all tested kinases) [1] - In HeLa cells stimulated with TNF-α (10 ng/mL), MK2 Inhibitor III (0.1-100 nM) dose-dependently suppressed phosphorylation of HSP27 (a direct MK-2 substrate), with an IC50 of 4.5 nM (western blot quantification) [1] - At 10 nM, MK2 Inhibitor III reduced TNF-α-induced HSP27 phosphorylation by ~88% compared to stimulated control, without affecting total HSP27 protein levels [1] - The inhibition of MK-2 by MK2 Inhibitor III was reversible: washout of the compound from TNF-α-stimulated HeLa cells restored HSP27 phosphorylation to ~75% of control levels within 2 hours [1] |
| ln Vivo |
The tracking LPS (rLPS) model shows a 20% reduction in TNFα production when MK2-IN-3 (Compound 16) (20 mg/kg; single pass prior to LPS challenge) is used [1].
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| Enzyme Assay |
Radiometric kinase assay: Recombinant human MK-2 protein was diluted in kinase buffer and mixed with serial dilutions of MK2 Inhibitor III (0.001-10 μM). The reaction mixture was supplemented with [γ-32P]ATP (at Km concentration for MK-2) and a synthetic peptide substrate (derived from HSP27, containing the MK-2 phosphorylation site). After incubation at 30°C for 40 minutes, the reaction was terminated by spotting onto phosphocellulose filters. Filters were washed to remove unincorporated radioactivity, and bound radioactivity (indicating phosphorylated substrate) was measured by scintillation counting. IC50 values were calculated from dose-response inhibition curves [1]
- Surface Plasmon Resonance (SPR) assay: MK-2 protein was immobilized on a sensor chip. MK2 Inhibitor III (serial dilutions: 0.0005-5 μM) was injected over the chip surface at a constant flow rate. Binding affinity (Ki) was determined by fitting the sensorgram data to a 1:1 binding model, accounting for ligand depletion [1] |
| Cell Assay |
HSP27 phosphorylation assay (western blot): HeLa cells were seeded in 6-well plates (2×105 cells/well) and cultured overnight. Cells were pre-treated with MK2 Inhibitor III (0.1-100 nM) for 1 hour, then stimulated with TNF-α (10 ng/mL) for 30 minutes. Cells were lysed in RIPA buffer, and proteins were separated by SDS-PAGE, transferred to PVDF membranes. Membranes were probed with antibodies against phosphorylated HSP27 (p-HSP27, Ser82) and total HSP27 (loading control). Immunoreactive bands were visualized by chemiluminescence, and band intensity was quantified by densitometry to calculate inhibition efficiency [1]
- Kinase selectivity cell assay: HEK293T cells were transfected with expression plasmids for p38α, ERK1, JNK2, or Akt1. After 24 hours, cells were treated with MK2 Inhibitor III (10 μM) for 1 hour, then stimulated with appropriate agonists (EGF for ERK1/Akt1, anisomycin for p38α/JNK2). Cell lysates were analyzed by western blot using phospho-specific antibodies for each kinase, confirming no significant inhibition of non-target kinases [1] |
| References | |
| Additional Infomation |
MK2 inhibitor III is a pyrrolopyridine small molecule inhibitor that binds to the ATP-binding pocket of MK-2 and acts as a competitive inhibitor of ATP binding [1]. The chemical structure of MK2 inhibitor III is based on pyrrolopyridine and is replaced by cyanophenyl and carboxamide groups, thereby optimizing its high affinity and selectivity for MK-2 [1]. MK-2 is a downstream effector molecule of the p38 MAPK pathway, and the inhibitory effect of MK2 inhibitor III on it can block the pro-inflammatory response mediated by this pathway (e.g., HSP27 phosphorylation, cytokine production) [1]. The compound has good water solubility (≥100 μM in PBS buffer at pH 7.4) and chemical stability under physiological conditions, making it suitable for in vitro biological experiments [1].
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| Molecular Formula |
C21H16N4O
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|---|---|
| Molecular Weight |
340.37794
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| Exact Mass |
340.132
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| Elemental Analysis |
C, 74.10; H, 4.74; N, 16.46; O, 4.70
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| CAS # |
724711-21-1
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| Related CAS # |
MK2-IN-3 hydrate;1186648-22-5
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| PubChem CID |
10389239
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| Appearance |
Off-white to gray solid powder
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| LogP |
3.588
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
26
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| Complexity |
526
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| Defined Atom Stereocenter Count |
0
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| SMILES |
N1C2C(=CC=CC=2)C=C(C2C=C(C3NC4=C(C(=O)NCC4)C=3)C=CN=2)C=1
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| InChi Key |
OWFLADWRSCINST-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H16N4O/c26-21-16-11-20(25-18(16)6-8-23-21)14-5-7-22-19(10-14)15-9-13-3-1-2-4-17(13)24-12-15/h1-5,7,9-12,25H,6,8H2,(H,23,26)
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| Chemical Name |
2-(2-quinolin-3-ylpyridin-4-yl)-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridin-4-one
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| Synonyms |
MK2 Inhibitor III; OUN11211; OUN 11211; OUN-11211
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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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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) |
DMSO: ~68 mg/mL (~199.8 mM)
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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 | 2.9379 mL | 14.6895 mL | 29.3789 mL | |
| 5 mM | 0.5876 mL | 2.9379 mL | 5.8758 mL | |
| 10 mM | 0.2938 mL | 1.4689 mL | 2.9379 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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