| Size | Price | Stock | Qty |
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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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| 500mg |
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| Other Sizes |
Purity: ≥98%
MK2-IN-1 is a novel, potent, non-ATP competitive and selecitve MAPKAPK2(MK2) inhibitor(IC50=0.11 uM). When MK2-IN-1 was screened against a large panel of 150 protein kinases at a concentration of 10 μM for kinase selectivity, only CK1γ3 was significantly inhibited at a concentration of greater than 50%. The human THP1 acute monocytic leukemia cell line secreted pro-inflammatory cytokines less frequently as a result of MK2-IN-1, which in turn reduced the amount of TNFα and IL6 that LPS could trigger. The SW1353 chondrosarcoma cell line and primary human chondrocyte cultures both secreted MMP13 when IL1β was stimulated, and MK2-IN-1 dose-dependently inhibited this. Our data indicate that MK2-IN-1 may be an excellent pharmacologic tool for specifically examining and validating MK2 biology, which is noteworthy given its high level of selectivity.
| Targets |
MK2 (IC50 = 0.11 μM)
Addition of the MK2 inhibitor MK2-IN-1 induced more alkaline phosphatase (AP)-positive colonies than the other factors in a short time , implying that MK2 may be responsible for the phosphorylation of Tfcp2l1.[2] 46C mESCs were treated with MK2-IN-1 for a period of time. The Tfcp2l1 protein level gradually increased without a change in the Tfcp2l1 transcript level within 2 h .[2] |
|---|---|
| ln Vitro |
Addition of the MK2 inhibitor MK2-IN-1 induced more alkaline phosphatase (AP)-positive colonies than the other factors in a short time , implying that MK2 may be responsible for the phosphorylation of Tfcp2l1.[2]
46C mESCs were treated with MK2-IN-1 for a period of time. The Tfcp2l1 protein level gradually increased without a change in the Tfcp2l1 transcript level within 2 h .[2] Treatment of 46C mESCs with 5 µM MK2-IN-1 for 0.5, 1, and 2 hours gradually increased Tfcp2l1 protein levels without altering its transcript levels[2] In 46C mESCs cultured in serum medium supplemented with 10 U/mL LIF, addition of 2 µM MK2-IN-1 for 6 days delayed mESC differentiation, increased Oct4 protein level, and inhibited the expression of differentiation markers Gata4 and Gata6[2] Inhibition of MK2 with MK2-IN-1 enhanced the ability of Tfcp2l1 to reprogram mouse EpiSCs into naïve pluripotent cells[2] MK2-IN-1 treatment did not significantly affect the generation of induced pluripotent stem cells from mouse fibroblast cells[2] |
| Enzyme Assay |
The enzymatic activity of recombinant human MK2 (kinase domain, Gln41-Thr338) was measured. The assay conditions included 2.5 nM MK2, 100 µM ATP, and varying concentrations (0–200 µM) of a peptide substrate (Acam peptide). The mode of inhibition for the initial hit compound 1 was determined by globally fitting the kinetic data to various models using the Akaike information criteria (AICc), identifying a noncompetitive inhibition model as most likely. This assay format was used to determine IC50 values for inhibitor compounds, including 25. [4]
A kinase selectivity profile for 25 was obtained by screening at a concentration of 10 µM against a panel of 150 protein kinases. Inhibition was considered significant if greater than 50%. [4] Cytochrome P450 (CYP) enzyme inhibition was assessed for 25 at concentrations up to 30 µM against a panel of CYP enzymes, and no inhibition was observed. [4] |
| Cell Assay |
46C mESCs were treated with 5 µM MK2-IN-1 for the indicated time periods (0.5, 1, 2 hours) and analyzed by Western blot for Tfcp2l1 protein levels[2]
For alkaline phosphatase (AP) staining, 46C mESCs were cultured in serum medium supplemented with 10 U/mL LIF and treated with 2 µM MK2-IN-1 for 6 days, then fixed and stained for AP activity[2] For reprogramming assay, mouse EpiSCs were treated with MK2-IN-1 under reprogramming conditions and assessed for AP-positive colony formation[2] |
| ADME/Pharmacokinetics |
In oral pharmacokinetic studies in rats, the area under the curve (AUC) of compound 25 (single dose of 10 mg/kg) was 2300 nM·h. [4] At concentrations up to 30 µM, compound 25 showed no inhibitory effect on a range of cytochrome P450 (CYP) enzymes. [4]
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| Toxicity/Toxicokinetics |
In vitro toxicity tests showed that the cytotoxicity (CC50) at 25 µM was greater than that at 20 µM. [4]
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| References | |
| Additional Infomation |
MK2-IN-1 has been used as a tool compound to inhibit MK2 activity and to investigate its role in the phosphorylation and degradation of Tfcp2l1 in mouse embryonic stem cells [2]. The inhibition of MK2 by MK2-IN-1 reduces the interaction between Tfcp2l1 and β-TrCP1, thereby stabilizing the Tfcp2l1 protein and promoting the self-renewal of mouse embryonic stem cells [2]. In addition, when MK2 is inhibited, MK2-IN-1 treatment also increases the phosphorylation level of serine residues in Tfcp2l1 [2].
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| Molecular Formula |
C27H25CLN4O2
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|---|---|
| Molecular Weight |
472.966005086899
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| Exact Mass |
472.166
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| CAS # |
1314118-92-7
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| Related CAS # |
MK2-IN-1 hydrochloride;1314118-94-9
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| PubChem CID |
53475321
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
699.2±55.0 °C at 760 mmHg
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| Flash Point |
376.7±31.5 °C
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| Vapour Pressure |
0.0±2.2 mmHg at 25°C
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| Index of Refraction |
1.643
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| LogP |
2.69
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
34
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| Complexity |
645
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(C1=CC=C(C2=CC=C(Cl)C=C2)O1)N(C3=CC=C(N4CCNCC4)C=C3)CC5=NC=CC=C5
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| InChi Key |
LIPNXDIBECKOMJ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C27H25ClN4O2/c28-21-6-4-20(5-7-21)25-12-13-26(34-25)27(33)32(19-22-3-1-2-14-30-22)24-10-8-23(9-11-24)31-17-15-29-16-18-31/h1-14,29H,15-19H2
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| Chemical Name |
5-(4-chlorophenyl)-N-(4-piperazin-1-ylphenyl)-N-(pyridin-2-ylmethyl)furan-2-carboxamide
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| Synonyms |
MK2-IN-1; MK2-IN 1; MK2 IN-1; MK25; MK-25; MK 25; MK2 Inhibitor IV; MK2 Inhibitor-IV
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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) |
DMSO: ~100 mg/mL (~196.3 mM)
Ethanol: ~2 mg/mL (~3.9 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 | 2.1143 mL | 10.5715 mL | 21.1430 mL | |
| 5 mM | 0.4229 mL | 2.1143 mL | 4.2286 mL | |
| 10 mM | 0.2114 mL | 1.0571 mL | 2.1143 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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