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.

Mixed Lineage Kinase Related Products (14):

Cat. No. Product Name Effect Purity
  • 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.
  • HY-12599
    URMC-099
    Inhibitor 99.07%
    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.
  • 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 (IC50=2 nM). GW806742X retards MLKL membrane translocation and inhibits necroptosis.
  • 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 (IC50=2 nM). GW806742X hydrochloride retards MLKL membrane translocation and inhibits necroptosis.
  • 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.
  • HY-148366
    NecroIr2
    Activator
    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.
  • HY-148365
    NecroIr1
    Activator
    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 CDK4 expression.
  • HY-151542
    MLKL-IN-4
    Inhibitor
    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.
  • 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.
  • HY-141889
    MLKL-IN-2
    Inhibitor 99.83%
    MLKL-IN-2 is a MLKL inhibitor extracted from patent WO2021224505A1, compound (i).
  • 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.
  • HY-100573S
    Necrosulfonamide-d4
    Inhibitor
    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.
  • 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.
  • HY-139878
    MLKL-IN-1
    Inhibitor
    MLKL-IN-1 is a covalent MLKL inhibitor with a KD of 50 μM.