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

Mixed Lineage Kinase

MLKs

Mixed Lineage Kinase

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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 99.47%
    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-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-15323
    PRT062607 Hydrochloride
    		Inhibitor 98.07%
    PRT062607 (P505-15) Hydrochloride is an orally available Syk inhibitor (IC50: 1 nM) that inhibits inflammation and induction Apoptosis. PRT062607 Hydrochloride exerts potent antitumor activity in tumor xenograft mouse models.
    PRT062607 Hydrochloride
  • 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-169509
    Topoisomerase I/II inhibitor 8
    		Activator
    Topoisomerase I/II Inhibitor 8 (Compound Ru7) is a dual catalytic inhibitor of Topoisomerase I/II, capable of inducing DNA damage and PARP-1 activation, which subsequently leads to the activation of RIPK1, RIPK3, and MLKL, ultimately triggering necroptosis. Topoisomerase I/II Inhibitor 8 demonstrates remarkable anticancer activity by effectively targeting the nuclei of cancer cells and inducing cell death through necroptosis, showing great clinical potential in circumventing drug resistance in cancer treatment.
    Topoisomerase I/II inhibitor 8
  • HY-170486
    MLK3-IN-1
    		Inhibitor
    MLK3-IN-1 (Compound 37) is a selective inhibitor for mixed-lineage protein kinase 3 (MLK3) with an IC50 <1 nM. MLK3-IN-1 inhibits FAK with an IC50 of 15.5 μM. MLK3-IN-1 exhibits good metabolic stability in mouse and human liver microsomes.
    MLK3-IN-1
  • HY-173075
    Anticancer agent 267
    		Activator
    Anticancer agent 267 (Compound 5q) is the activator for RIPK3 and MLKL. Anticancer agent 267 inhibits the proliferation in a variety of cancer cell lines (IC50 for MDA-MB-231, MDA-MB-486 and MCF-7 is 9.79, 10.77 and 5.94 μM, respectively), arrests cell cycle at subG1 phase, and induces necroptosis in cell MDA-MB-231. Anticancer agent 267 exhibits antitumor activity in mouse xenograft models.
    Anticancer agent 267
  • HY-101524
    TC13172
    		Inhibitor 99.04%
    TC13172 is a mixed lineage kinase domain-like protein (MLKL) inhibitor with an EC50 value of 2 nM for HT-29 cells.
    TC13172
  • HY-112274
    M443
    		98.95%
    M443 is an irreversible and specific inhibitor of MRK, with an IC50<125 nM.
    M443
  • 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-148907
    CS640
    		Inhibitor 99.43%
    CS640 is a selective inhibitor of calmodulin-dependent kinases. CS640 inhibits CaMK1D, CaMK1B, CaMK1A, CaMK1G, PIP5K1C, MEK5, RIPK4 and MLK3 with IC50 values of 0.08, 0.03, 0.001, 0.001, 11.2, 0.025, 5.69 and 2.75 μM, respectively. CS640 also shows inhibitory effects to CYP450 2C9 and CYP450 2C19 with IC50 values of 6 and 10 μM, respectively.
    CS640
  • HY-111351
    MLK-IN-1
    		Inhibitor 99.07%
    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). As an inhibitor of MDM4, CEP-1347 can more effectively inhibit the growth of glioma cells expressing wild-type p53.
    CEP-1347
  • HY-156119
    MLKL-IN-6
    		Inhibitor 98.57%
    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-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-141889
    MLKL-IN-2
    		Inhibitor 99.45%
    MLKL-IN-2 is a MLKL inhibitor extracted from patent WO2021224505A1, compound (i).
    MLKL-IN-2
  • HY-156591
    PROTAC MLKL Degrader-1
    		Degrader 99.76%
    PROTAC MLKL Degrader-1 (Compound 36) is a PROTAC degrader of MLKL, with a Dmax ＞90%. PROTAC MLKL Degrader-1 contains modified CRBN ligands, linker and Lenalidomide (HY-A0003)-linker fragments. PROTAC MLKL Degrader-1 abrogates cell death in a TSZ model of necroptosis.
    PROTAC MLKL Degrader-1
  • HY-15324
    PRT062607 acetate
    		Inhibitor 99.83%
    PRT062607 (P505-15) acetate is an orally available Syk inhibitor (IC50: 1 nM) that inhibits inflammation and induction Apoptosis. PRT062607 acetate exerts potent antitumor activity in tumor xenograft mouse models..
    PRT062607 acetate
  • 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
Cat. No. Product Name / Synonyms Application Reactivity