MLKL-IN-4
MLKL-IN-4 (compound 56) is a potent MLKL (Mixed lineage kinase domain-like protein) inhibitor. MLKL-IN-4 inhibits necroptosis in HT-29 cells and acts downstream of MLKL phosphorylation, with EC50 of 82 nM. MLKL-IN-4 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.
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- CAS 番号: 3031406-17-1
- 分子式: C30H27ClN4O5
- 分子量:559.01
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保管条件:
Please store the product under the recommended conditions in the Certificate of Analysis.
生物活性
製品説明
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| HT-29 | EC50 |
>10 μM
Compound: 56
|
Anti-necroptic activity in human HT-29 cells assessed as inhibition of TSZ induced necroptosis incubated for 5 min followed by compound washout and further induced with TSZ by celltiter-glo luminescent cell viability assay
Anti-necroptic activity in human HT-29 cells assessed as inhibition of TSZ induced necroptosis incubated for 5 min followed by compound washout and further induced with TSZ by celltiter-glo luminescent cell viability assay
|
[PMID: 36136378] |
| HT-29 | EC50 |
180.3 nM
Compound: 56
|
Anti-necroptic activity in human HT-29 cells assessed as inhibition of TSZ induced necroptosis incubated for 3 hr followed by compound washout and further induced with TSZ by celltiter-glo luminescent cell viability assay
Anti-necroptic activity in human HT-29 cells assessed as inhibition of TSZ induced necroptosis incubated for 3 hr followed by compound washout and further induced with TSZ by celltiter-glo luminescent cell viability assay
|
[PMID: 36136378] |
| HT-29 | EC50 |
188.1 nM
Compound: 56
|
Anti-necroptic activity in human HT-29 cells assessed as inhibition of TSZ induced necroptosis incubated for 3 hrs followed by TSZ stimulation by celltiter-glo luminescent cell viability assay
Anti-necroptic activity in human HT-29 cells assessed as inhibition of TSZ induced necroptosis incubated for 3 hrs followed by TSZ stimulation by celltiter-glo luminescent cell viability assay
|
[PMID: 36136378] |
| HT-29 | EC50 |
584.3 nM
Compound: 56
|
Anti-necroptic activity in human HT-29 cells assessed as inhibition of TSZ induced necroptosis incubated for 1 hr followed by compound washout and further induced with TSZ by celltiter-glo luminescent cell viability assay
Anti-necroptic activity in human HT-29 cells assessed as inhibition of TSZ induced necroptosis incubated for 1 hr followed by compound washout and further induced with TSZ by celltiter-glo luminescent cell viability assay
|
[PMID: 36136378] |
| HT-29 | EC50 |
82 nM
Compound: 56
|
Anti-necroptic activity in human HT-29 cells assessed as inhibition of TSZ (TNFalpha, Smac mimetic and z-VAD-FMK) induced necroptosis incubated for 24 hrs by celltiter-glo luminescent cell viability assay
Anti-necroptic activity in human HT-29 cells assessed as inhibition of TSZ (TNFalpha, Smac mimetic and z-VAD-FMK) induced necroptosis incubated for 24 hrs by celltiter-glo luminescent cell viability assay
|
[PMID: 36136378] |
体外実験
MLKL-IN-4 (compound 56) (10 μM) slightly inhibits RIPK1, does not affect the phosphorylation status of RIPK1 and MLKL[1].
MLKL-IN-4 (1 μM, 24 h) inhibits the translocation of MLKL to cell membranes in HT-29 cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
体内実験
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
化学情報
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CAS 番号 3031406-17-1
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分子量 559.01
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分子式 C30H27ClN4O5
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SMILES
O=C(NC1=C(Cl)N(CC#CC2=CC=C(O)C(CN3C=CC=CC3=O)=C2)C(N(C)C1=O)=O)CCC4=CC=C(C)C=C4
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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
Please store the product under the recommended conditions in the Certificate of Analysis.
プロトコル
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Kinase activity and phosphorylation assays
Kinase activity assays measure the ability of kinases to transfer phosphate groups from ATP to specific substrates, while phosphorylation assays detect the presence and levels of phosphorylated proteins. Common methods include radiolabeled ATP incorporation (e. g. ,), ADP release detection via bioluminescence (e. g. ,[3]), enzyme-linked immunosorbent assays (ELISA) for phospho-specific epitopes (e. g. ,[6]), and microtiter-based formats for high-throughput screening (e. g. ,[8]). The ADP-Glo assay quantifies kinase activity by measuring ADP produced during phosphorylation using a luciferase-based system. Radiometric assays involve autoradiography or scintillation counting after incorporation of 32P-labeled ATP into substrate proteins. ELISA-based approaches rely on phospho-specific antibodies to detect activated kinases in cell lysates or purified samples.
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Western Blot
Western blotting (WB) is a commonly used experimental method in molecular biology, biochemistry, and immunogenetics for identifying and quantifying target proteins. It combines gel electrophoresis with immunoassay, enabling researchers to analyze protein expression, post-translational modifications, and molecular weight.
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EdU Incorporation Assay (Click Chemistry-Based DNA Synthesis Measurement)
The EdU incorporation assay measures DNA synthesis by adding the thymidine analog 5-ethynyl-2′-deoxyuridine to cells or tissues, where it is incorporated into newly synthesized DNA during S phase. Incorporated EdU is detected by copper-catalyzed azide-alkyne cycloaddition, in which a fluorescent azide covalently reacts with the ethynyl group on EdU, allowing S-phase cells to be detected by fluorescence microscopy, flow cytometry, or high-content imaging. EdU detection does not require DNA denaturation or anti-BrdU antibody access, which preserves sample structure and improves compatibility with immunostaining and multiparameter cytometry compared with BrdU-based detection. EdU can be cytotoxic in a cell-type- and exposure-dependent manner, so pulse duration, concentration, and continuous-labeling designs should be validated for each cell type.
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Protocol for Kinase activity and phosphorylation assays
Kinase activity assays measure transfer of phosphate from ATP to a protein or peptide substrate, generating phosphorylated substrate, ADP, or incorporated radiolabeled phosphate as the readout; phosphorylation assays measure site-specific phosphorylation in cells or tissues as a proxy for kinase-pathway activation, inhibition, or substrate regulation. Phosphorylation can be detected by phospho-specific Western blot, immunoprecipitation kinase assay, phospho-immunofluorescence, phospho-flow cytometry, luminescent ADP detection, radiolabeled ATP incorporation, or reporter-based pathway assays, and these readouts can be applied to cancer cells, primary neurons, mouse tumors, organoids, inflammatory macrophages, ferroptosis studies, and mitophagy studies when the kinase target is biologically relevant.
純度とドキュメンテーション
参考文献
Calculators
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)