1. Signaling Pathways
  2. MAPK/ERK Pathway
  3. Mixed Lineage Kinase

Mixed Lineage Kinase

MLKs

Mixed lineage kinases (MLKs) are mitogen activated protein kinase kinase kinases (MAPKKKs) with features of both serine-threonine and tyrosine kinases that regulate the c-Jun N-terminal kinase (JNK) mitogen activated protein kinase (MAPK) signaling cascade, and also regulate p38 and extracellular signal-regulated kinase (ERK).

MLK3 (MAP3K11) is the most widely expressed MLK family member, and is expressed in neurons (as well as other cell types). At the cellular level, MLK3 is activated by stress, including reactive oxygen species, ceramide, and TNFα. At the molecular level, it is activated by Cdc42 and Rac, which interact with MLK3, and can cause it to dimerize via a leucine zipper interface, resulting in autophosphorylation and enzyme activation.

Cat. No. Product Name Effect Purity Chemical Structure
  • HY-100573
    Necrosulfonamide
    Inhibitor 98.84%
    Necrosulfonamide is a necroptosis inhibitor acting by selectively targeting the mixed lineage kinase domain-like protein (MLKL). Necrosulfonamide prevents MLKL-RIP1-RIP3 necrosome complex from interacting with its downstream effectors. MLKL is a critical substrate of RIP3 during the induction of necrosis.
    Necrosulfonamide
  • HY-112292
    GW806742X
    Inhibitor 99.91%
    GW806742X, an ATP mimetic and a potent MLKL (Mixed Lineage Kinase Domain-Like protein) inhibitor, binds the MLKL pseudokinase domain with a Kd of 9.3 μM. GW806742X has activity against VEGFR2/KDR/Flk-1 (IC50=2 nM). GW806742X retards MLKL membrane translocation and inhibits necroptosis.
    GW806742X
  • HY-12599
    URMC-099
    Inhibitor 99.34%
    URMC-099 is an orally bioavailable and potent mixed lineage kinase type 3 (MLK3) (IC50=14 nM) inhibitor with with excellent blood-brain barrier penetration properties.
    URMC-099
  • HY-144828
    RIP1/RIP3/MLKL activator 1
    Activator
    RIP1/RIP3/MLKL activator 1 (Compound 6i) is a potent anti-glioma agent. RIP1/RIP3/MLKL activator 1 induces necroptosis through RIP1/RIP3/MLKL pathway. RIP1/RIP3/MLKL activator 1 exerts acceptable BBB permeability.
    RIP1/RIP3/MLKL activator 1
  • HY-112292A
    GW806742X hydrochloride
    Inhibitor 98.77%
    GW806742X hydrochloride, an ATP mimetic and a potent MLKL (Mixed Lineage Kinase Domain-Like protein) inhibitor, binds the MLKL pseudokinase domain with a Kd of 9.3 μM. GW806742X hydrochloride has activity against VEGFR2/KDR/Flk-1 (IC50=2 nM). GW806742X hydrochloride retards MLKL membrane translocation and inhibits necroptosis.
    GW806742X hydrochloride
  • HY-156119
    MLKL-IN-6
    Inhibitor
    MLKL-IN-6 (compound P28) is a mixed lineage kinase inhibitor targeting Mixed Lineage Kinase domain-like (MLKL). MLKL-IN-6 inhibits cell necrosis. MLKL-IN-6 inhibits MLKL phosphorylation and oligomerization during cell necrosis, inhibits immune cell death, and reduces the expression of adhesion factors. MLKL-IN-6 has low cytotoxicity, and it inhibits hepatic stellate cell activation, reduces liver fibrosis marker levels, and has anti-fibrotic effects.
    MLKL-IN-6
  • HY-149393
    RIPK3-IN-3
    Inhibitor
    RIPK3-IN-3 (compound 20) is a selective inhibitor of RIP kinase RIPK3 (IC50=10 nM). RIPK3 mediates the phosphorylation of Mixed Lineage Kinase (MLKL) and causes necroptosis, while RIPK3-IN-3 inhibits p-MLKL oligomerization and thereby inhibits necroptosis. RIPK3-IN-3 also downregulates CXCL5 secretion and inhibits AsPC-1 cell migration and invasion.
    RIPK3-IN-3
  • HY-101524
    TC13172
    Inhibitor 98.93%
    TC13172 is a mixed lineage kinase domain-like protein (MLKL) inhibitor with an EC50 value of 2 nM for HT-29 cells.
    TC13172
  • HY-111351
    MLK-IN-1
    Inhibitor 99.06%
    MLK-IN-1 is a potent, brain penetrant and specific mixed lineage kinase 3 (MLK-3) inhibitor, compound 68, extracted from patent US20140256733A1.
    MLK-IN-1
  • HY-10412
    CEP-1347
    Inhibitor 98.50%
    CEP-1347 is an inhibitor of the JNK/SAPK pathway with neuroprotective effects. CEP-1347 blocks JNK1 activation induced by members of the mixed lineage kinase (MLK) family (MLK3, MLK2, MLK1, dual leucine zipper kinase, and leucine zipper kinase). CEP-1347 also suppress MDM4 expression and activates wild-type p53 in retinoblastoma cells.
    CEP-1347
  • HY-148366
    NecroIr2
    Activator 98.99%
    NecroIr2 is an iridium(III) complex, serves as necroptosis inducers in Cisplatin (HY-17394)-resistant lung cancer cells (A549R). NecroIr2 selectively accumulates in mitochondria, leading to oxidative stress and loss of mitochondrial membrane potential (MMP). NecroIr2 activates receptor-interacting serine-threonine kinase 3 (RIPK3) and mixed lineage kinase domain-like pseudokinase (MLKL), and regulates CDK4 expression.
    NecroIr2
  • HY-148365
    NecroIr1
    Activator 98.02%
    NecroIr1 is an iridium(III) complex, serves as necroptosis inducers in Cisplatin (HY-17394)-resistant lung cancer cells (A549R). NecroIr1 selectively accumulates in mitochondria, leading to oxidative stress and loss of mitochondrial membrane potential (MMP). NecroIr1 activates receptor-interacting serine-threonine kinase 3 (RIPK3) and Mixed Lineage Kinase (MLKL), and regulates CDK/cdk4.html” class=”link-product” target=”_blank”>CDK4 expression.
    NecroIr1
  • HY-149258
    KWCN-41
    Inhibitor 99.83%
    KWCN-41 is a selective and efficient inhibitor of RIPK1 kinase with an IC50 value of 88 nM. KWCN-41 specifically inhibits cell necrosis but does not inhibit apoptosis. KWCN-41 also has anti-inflammatory effects.
    KWCN-41
  • HY-141889
    MLKL-IN-2
    Inhibitor 99.83%
    MLKL-IN-2 is a MLKL inhibitor extracted from patent WO2021224505A1, compound (i).
    MLKL-IN-2
  • HY-100573S
    Necrosulfonamide-d4
    Inhibitor 99.26%
    Necrosulfonamide-d4 is the deuterium labeled Necrosulfonamide. Necrosulfonamide is a necroptosis inhibitor acting by selectively targeting the mixed lineage kinase domain-like protein (MLKL). Necrosulfonamide prevents MLKL-RIP1-RIP3 necrosome complex from interacting with its downstream effectors. MLKL is a critical substrate of RIP3 during the induction of necrosis.
    Necrosulfonamide-d<sub>4</sub>
  • HY-149052
    SZM-1209
    Inhibitor
    SZM-1209 is an orally active, potent and specific RIPK1 inhibitor, with a Kd of 85 nM. SZM-1209 exhibits high anti-necroptotic activity (EC50=22.4 ± 8.1 nM). SZM-1209 shows anti-SIRS (systemic inflammatory response syndrome), and anti-ALI (acute lung injury) effects.
    SZM-1209
  • HY-151541
    MLKL-IN-3
    Inhibitor
    MLKL-IN-3 (compound 66) is a potent MLKL (Mixed lineage kinase domain-like protein) inhibitor. MLKL-IN-3 inhibits necroptosis in HT-29 cells and acts downstream of MLKL phosphorylation, with EC50 of 31 nM. MLKL-IN-3 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-3
  • HY-148767
    MLKL-IN-5
    Inhibitor
    MLKL-IN-5 is a potent MLKL inhibitor that mediates necroptosis.
    MLKL-IN-5
  • HY-100573A
    (E/Z)-Necrosulfonamide
    Inhibitor
    (E/Z)-Necrosulfonamide is a racemic compound of Necrosulfonamide (HY-100573). Necrosulfonamide is a necroptosis inhibitor acting by selectively targeting the mixed lineage kinase domain-like protein (MLKL). Necrosulfonamide prevents MLKL-RIP1-RIP3 necrosome complex from interacting with its downstream effectors. MLKL is a critical substrate of RIP3 during the induction of necrosis.
    (E/Z)-Necrosulfonamide
  • HY-139878
    MLKL-IN-1
    Inhibitor
    MLKL-IN-1 is a covalent MLKL inhibitor with a KD of 50 μM.
    MLKL-IN-1
Cat. No. Product Name / Synonyms Application Reactivity