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 MLKL and Gasdermin D (GSDMD) inhibitor, capable of separately inhibiting necroptosis and pyroptosis of cells. Necrosulfonamide does not affect the activation of upstream signals, but specifically inhibits the downstream executor oligomerization step. Necrosulfonamide reduces the expression of the key kinases NLRP3 and caspase-1 involved in necroptosis and pyroptosis, activate the Nrf2 pathway and the downstream antioxidant enzymes, and also downregulates a variety of inflammatory factors. Necrosulfonamide plays significant roles in various diseases such as neurodegenerative diseases (such as Parkinson’s disease), tissue damage and ischemia-reperfusion injury, inflammatory bowel disease, osteoarthritis and fracture repair, and hair loss by regulating two important programmed necrosis pathways.
    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 (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-112274
    M443
    		99.92%
    M443 is an irreversible and specific inhibitor of MRK, with an IC50<125 nM.
    M443
  • 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-177119
    ZBP1 Covalent PROTAC-1
    		Inhibitor
    ZBP1 Covalent PROTAC-1 is a covalent Z-DNA binding protein 1 ZBP1 PROTAC degrader, with its DC50 being 25.69 nM. ZBP1 Covalent PROTAC-1 integrates the ligand that recruits the VHL E3 ubiquitin ligase and the DNA aptamer (Aptamer Z3) with the specific Zα domain that can bind to ZBP1, which has a high affinity (KD = 2.71 nM) with ZBP1. After degrading ZBP1, the phosphorylation levels of downstream signaling molecules RIPK3 and MLKL significantly decrease. ZBP1 Covalent PROTAC-1, encapsulated by nano-liposomes, significantly improves the survival rate of mice infected with influenza A virus (IAV) after administration via the trachea.
    ZBP1 Covalent PROTAC-1
  • HY-179680
    RIPK1-IN-38
    		Inhibitor
    RIPK1-IN-38 is an orally active RIPK1 inhibitor with an IC50 value of 27 nM. RIPK1-IN-38 can inhibit the phosphorylation of RIPK1 and its downstream signaling molecules RIPK3 and MLKL. RIPK1-IN-38 exhibits anti-necroptotic activity. RIPK1-IN-38 has excellent anti-inflammatory efficacy in both the SIRS model and GVHD model. RIPK1-IN-38 can be used for the research of inflammatory and immune-related diseases.
    RIPK1-IN-38
  • HY-183538
    Necroptosis inducer 2
    		Activator
    Necroptosis inducer 2 is a necroptosis inducer and copper chelator. Necroptosis inducer 2 chelates intracellular free copper ions, disrupts redox homeostasis, elevates ROS levels, disrupts mitochondrial membrane potential, and induces cancer cell necroptosis. Necroptosis inducer 2 upregulates the necroptosis markers p-MLKL and p-RIP3 expression. Necroptosis inducer 2 exhibits anti-tumor activity in mice. Necroptosis inducer 2 can be used for the research of cancer, such as triple-negative breast cancer.
    Necroptosis inducer 2
  • 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-12599
    URMC-099
    		Inhibitor 98.69%
    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-148907
    CS640
    		Inhibitor 99.48%
    CS640 (Compound 19) is a chemical probe and a calmodulin-dependent kinase inhibitor. CS640 inhibits CaMK1D, CaMK1B, CaMK1A, CaMK1G, MEK5, RIPK4, mLK3 and PIP5K1, with IC50 values of 8, 3, 1, 1, 25 nM, 5.69, 2.75 and 11.2 μM, respectively. CS640 blocks Aβ-induced hyperphosphorylation of tau protein at the Thr181 site, but fails to protect primary mouse cortical neurons from Aβ-induced toxic damage. CS640 is applicable to research related to Alzheimer's disease.
    CS640
  • HY-162424
    ZBP1/RIP3/MLKL activator 1
    		Activator 99.73%
    ZBP1/RIP3/MLKL activator 1 (compound 3a) is a synthetically derived quinoline compound. ZBP1/RIP3/MLKL Activator 1 induces DNA damage, enhances intracellular levels of reactive oxygen species (ROS), and triggers apoptosis via the caspase pathway. Furthermore, when apoptosis is inhibited, ZBP1/RIP3/MLKL Activator 1 promotes necroptotic cell death through the ZBP1-RIP3-MLKL pathway. ZBP1/RIP3/MLKL Activator 1 is utilized in oncological research, particularly in the selective targeting of cells with impaired apoptotic function.
    ZBP1/RIP3/MLKL activator 1
  • 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-N2909
    Aurantiamide
    		Inhibitor 99.56%
    Aurantiamide is a non-covalent, orally active, blood-brain-permeable GRPR selective antagonist with anti-inflammatory and neuroprotective effects. Aurantiamide reduces inflammation and oxidative stress in renal tissue by inhibiting GRPR-mediated renal necrosis pathways (such as RIPK3/MLKL signaling) and NF-κB inflammatory pathways, exerting anti-acute kidney injury and endothelial function activities. Aurantiamide also inhibits the M1 polarization of microglia and inhibits NLRP3 activation, thereby improving AD mouse models. Aurantiamide has in vivo inhibitory efficacy in acute kidney injury models such as ischemia/reperfusion, sepsis, and hypertension models.
    Aurantiamide
  • HY-168972
    Famlasertib
    		Inhibitor 99.94%
    Famlasertib is a potent, brain-penetrant MAP4K inhibitor with IC50s value of 0.3 nM, 23.7 nM, and 44.7 nM for HGK (MAP4K4), MLK3, and MLK1, respectively. Famlasertib shows motor neuron protection and anti-inflammatory properties. Famlasertib can be used for the study of amyotrophic lateral sclerosis (ALS).
    Famlasertib
  • HY-N0546
    Ligustroflavone
    		Inhibitor 99.90%
    Ligustroflavone is an orally active flavonoid compound. Ligustroflavone can be extracted from Ligustrum lucidum. Ligustroflavone antagonizes the calcium-sensing receptor (CaSR), inhibits the RIPK1/RIPK3/MLKL pathway, and downregulates TGF-β/Smad signaling. Ligustroflavone regulates calcium metabolism, protects bone tissue, reduces cerebral ischemic injury, and inhibits liver fibrosis. Ligustroflavone can be used in the study of diabetic osteoporosis, ischemic stroke, and liver fibrosis.
    Ligustroflavone
  • HY-112292A
    GW806742X hydrochloride
    		Inhibitor 98.30%
    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.
    GW806742X hydrochloride
  • 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-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-141889
    MLKL-IN-2
    		Inhibitor 99.45%
    MLKL-IN-2 is a MLKL inhibitor extracted from patent WO2021224505A1, compound (i).
    MLKL-IN-2
Cat. No. Product Name / Synonyms Application Reactivity