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^[1]. 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.

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.

MLKL-IN-4 (compound 56) shows T1/2 over 48 h and more than 150-fold lower reaction rates with glutathione (GSH), which potentially decreased their off-target effects and cell toxicity^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

559.01

C₃₀H₂₇ClN₄O₅

3031406-17-1

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

Room temperature in continental US; may vary elsewhere.

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• [1]. Cui B, et al. Discovery of a New Class of Uracil Derivatives as Potential Mixed Lineage Kinase Domain-like Protein (MLKL) Inhibitors. J Med Chem. 2022 Oct 13;65(19):12747-12780.  [Content Brief]