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.
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Mixed Lineage Kinase Related Products (59)
Related Products (59)
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Antibodies (3)
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RIPK1-IN-17
0 ImagesCat. No.: HY-157039CAS No.: 3033385-59-7RIPK1-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).
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PRT062607 acetate
0 ImagesSynonyms: P505-15 acetate; PRT-2607 acetate; BIIB-057 acetate
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CEP-1347
0 ImagesSynonyms: KT7515CEP-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.
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RIPK3-IN-3
0 ImagesCat. No.: HY-149393CAS No.: 3052303-53-1RIPK3-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.
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(E/Z)-Necrosulfonamide
0 Images(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.
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RETRA
0 ImagesRETRA is a RIPK1/RIPK3/MLKL and p73 activator. RETRA mediates plasma membrane disruption, induces ROS accumulation, triggers early mitochondrial hyperpolarization, and synergistically drives necroptosis. RETRA inhibits cancer cells carrying mutant p53 via a p73-dependent salvage pathway. RETRA can be used in research related to cervical cancer and cancers with mutant p53.
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MBA-m1
0 ImagesMBA-m1 is a reversible non-covalent allosteric inhibitor of mMLKL2, with a Kd value of 6 μM for mMLKL2. MBA-m1 delays Necroptosis. MBA-m1 has no effect on the activities of RIPK1 or RIPK3. MBA-m1 alleviates skin injury, epidermal thickening and immune cell infiltration in dermatitis models, and reduces aortic diameter enlargement and structural changes in abdominal aortic aneurysm models. MBA-m1 can be used in research related to dermatitis and abdominal aortic aneurysm.
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Necrosulfonamide-d4
0 ImagesNecrosulfonamide-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.
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NecroIr2
0 ImagesCat. No.: HY-148366Purity: 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.
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NecroIr1
0 ImagesCat. No.: HY-148365Purity: 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.
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(E)-2-Hexadecenal
0 ImagesSynonyms: 16:1 Aldehyde; trans-2-Hexadecenal(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.
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MLK-IN-2
0 ImagesMLK-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.
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CEP1347-VHL-02
0 ImagesCat. No.: HY-168026CEP1347-VHL-02 is a selective MLK3 PROTAC degrader that mediates MLK3 degradation via the ubiquitin-proteasome system, with a DC50 of 50-300 nM. After degrading MLK3, CEP1347-VHL-02 inhibits downstream JNK signaling, induces G2/M phase arrest and apoptosis in cancer cells, and suppresses their clonogenic, migratory and 3D sphere-forming abilities. CEP1347-VHL-02 can be used for the research of triple-negative breast cancer.
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Topoisomerase I/II inhibitor 8
0 ImagesCat. No.: HY-169509CAS No.: 355400-87-2Topoisomerase 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.
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Zharp1-163
0 ImagesCat. No.: HY-178163Zharp1-163 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.
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RIPK1-IN-34
0 ImagesCat. No.: HY-178464CAS No.: 3065634-19-4RIPK1-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).
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RIPK1-IN-38
0 ImagesCat. No.: HY-179680CAS No.: 3092834-30-2RIPK1-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.
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MLK3-IN-1
0 ImagesCat. No.: HY-170486CAS No.: 3104123-06-7MLK3-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.
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SZM-1209
0 ImagesCat. No.: HY-149052CAS No.: 2919801-86-6SZM-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.
