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

Mixed Lineage Kinase

MLKs

Mixed Lineage Kinase

Related Products

PDF 0.17 MB

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-157039
    RIPK1-IN-17
    		Inhibitor
    RIPK1-IN-17 is an orally active, selective RIPK1 inhibitor (Kd = 17 nM) and shows no significant inhibition to RIPK3. RIPK1-IN-17 specifically inhibits necroptosis rather than apoptosis by inhibiting RIPK1, RIPK3, and MLKL phosphorylation. RIPK1-IN-17 protects mice from hypothermia and death. RIPK1-IN-17 can be used for the study of necroptosis-related diseases such as inflammatory response syndrome (SIRS).
    RIPK1-IN-17
  • 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-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-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-100573A
    (E/Z)-Necrosulfonamide
    		Inhibitor 98.03%
    (E/Z)-Necrosulfonamide is a racemic compound of Necrosulfonamide (HY-100573). 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.
    (E/Z)-Necrosulfonamide
  • HY-148365
    NecroIr1
    		Activator 98.53%
    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.
    NecroIr1
  • HY-24504
    MBA-m1
    		Inhibitor 98.20%
    MBA-m1 is a MLKL inhibitor. MBA-m1 inhibits necroptosis in Mlkl−/− NIH-3T3 cells. MBA-m1 ameliorates disease in MLKL-induced dermatitis and abdominal aortic aneurysm mouse model.
    MBA-m1
  • 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-100573S
    Necrosulfonamide-d4
    		Inhibitor 99.65%
    Necrosulfonamide-d4 is the deuterium labeled Necrosulfonamide (HY-100573). 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-d<sub>4</sub>
  • HY-148366
    NecroIr2
    		Activator 98.02%
    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-121683
    (E)-2-Hexadecenal
    		Activator 99.9%
    (E)-2-Hexadecenal (trans-2-Hexadecenal) is an MLK3 activator that induces cytoskeletal remodeling, leading to cell rounding, detachment, and ultimately apoptosis in human and mouse cells. (E)-2-Hexadecenal activates the MLK3 signaling pathway, phosphorylating MKK4/7 and JNK, subsequently activating downstream targets of JNK, such as c-Jun phosphorylation, cytochrome c release, Bax activation, Bid cleavage, and Bim translocation to mitochondria. (E)-2-Hexadecenal has potential applications in research related to sphingolipid signaling pathways.
    (E)-2-Hexadecenal
  • HY-161271
    MLK-IN-2
    		Inhibitor 98.22%
    MLK-IN-2 (Compound 9a) is a Mixed Lineage Kinase 3 (MLK3) inhibitor containing 3H-imidazole [4,5-b] pyridine structure. IC50 value is 6 nM. MLK-IN-2 can be used to study cancer and neurodegenerative diseases.
    MLK-IN-2
  • HY-168026
    CEP1347-VHL-02
    CEP1347-VHL-02 is a PROTAC targeting MLK3. CEP1347-VHL-02 consists of PROTAC target protein ligand CEP-1347 (HY-10412) (red part), E3 ubiquitin ligase ligand (S,R,S)-AHPC-Me (HY-112078) (blue part) and PROTAC Linker Amino-PEG3-CH2COOH (HY-140189) (black part), of which the target protein ligand activity control is CEP-1347-acid (HY-168027), and the conjugate of E3 ubiquitin ligase ligand + Linker is (S,R,S)-AHPC-Me-CO-CH2-PEG3-NH2 (HY-131387)[1].
    CEP1347-VHL-02
  • 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-178163
    Zharp1-163
    		Inhibitor
    Zharp1-163 is a dual inhibitor of ferroptosis and necroptosis. Zharp1-163 effectively blocks ferroptosis by reducing reactive oxygen species (ROS) levels and inhibits necroptosis by potently and selectively targeting RIPK1 kinase activity (KD = 240 nM; IC50 = 406.1 nM). Zharp1-163 inhibits the cellular activation of RIPK1, RIPK3 and MLKL in response to necroptotic stimulation. Zharp1-163 markedly attenuates TNF-α (HY-P1875)-induced systemic inflammatory syndrome, including the prevention of TNF-α-induced mortality and hypothermia in mice. Zharp1-163 significantly alleviates acute kidney injury associated with both necroptosis and ferroptosis in models induced by Cisplatin (HY-17394) and ischemia-reperfusion. Zharp1-163 can be used for the study of diseases associated with cell death pathways, such as kidney disease.
    Zharp1-163
  • HY-178464
    RIPK1-IN-34
    		Inhibitor
    RIPK1-IN-34 is a selective, brain-penetrant RIPK1 inhibitor (IC50 = 126.70 nM) with almost no inhibitory effect on RIPK3 (IC50 ＞ 10, 000 nM). RIPK1-IN-34 offers substantial neuroprotection by inhibiting the phosphorylation of RIPK1, RIPK3, and mixed lineage kinase domain-like pseudokinase (MLKL) within the necroptosis pathway. RIPK1-IN-34 shows the neuroprotective effect in a rat middle cerebral artery occlusion (MCAO) model. RIPK1-IN-34 can be used for the study of anti-acute ischemic stroke (AIS).
    RIPK1-IN-34
  • 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-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-E70800
    Biotin-MLK2 Recombinant Human Active Protein Kinase
    MLK2 is a kinase for phosphorylation of H3 at threonine 3 and is associated with the osmotic stress response. MLK2 is involved in multiple signaling pathways in the developmental process. Biotin-MLK2 Recombinant Human Active Protein Kinase is obtained by expressing MLK2 proteins and is biotinylated.
    Biotin-MLK2 Recombinant Human Active Protein Kinase
  • 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
Cat. No. Product Name / Synonyms Application Reactivity