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Request The Product List ofMixed Lineage Kinase (MLK) Mixed Lineage Kinase (MLK)

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 CAS No. Information



A small molecule covalent inhibitor of mixed lineage kinase domain like protein (MLKL) that specifically blocks necrosis downstream of RIP3 activation; binds within the N-terminal 178 residues of human MLKL; arrests necrosis at a specific step at which RIP3 formed discrete punctae in cells.




GW806742X is a small molecule MLKL (Mixed Lineage Kinase Domain-Like) interactor that binds the MLKL pseudokinase domain (Kd=9.3 uM), retards membrane association to inhibit necroptosis; rescues 50% of wild-type MDFs from TSQ-induced necroptosis with IC50 <50 nM, with >50-fold greater potency than Nec-1; enhances RIPK3-mediated phosphorylation of MLKL (S345 and S347) at 10 uM.




URMC-099 is a potent, orally bioavailable, brain penetrant inhibitor of mixed lineage kinase 3 (MLK3) with IC50 of 14 nM; shows >90% inhibition against 111 kinases in a panel of 442 kinases at 1 uM; URMC-099 likely functions in HIV-1 associated neurocognitive disorders (HAND) preclinical models by inhibiting multiple kinase pathways, including MLK3 and LRRK2 (IC50=11 nM); inhibits LPS-induced TNFα release in microglial cells, HIV-1 Tat-induced release of cytokines in human monocytes and up-regulation of phospho-JNK in Tat-injected brains of mice.




CEP-1347 (KT-7515) is a potent and selective MLK inhibitor that completely rescues motoneurons and inhibits JNK1 activation with IC50 of 20 nM; has weak inhibitory activity for Trk A and MLCK; promotes motoneuron survival and simultaneously inhibits the JNK1 signaling cascade; inhibits recombinant MLK1/2/3 with IC50 of 23-51 nM; blocks cell death (overexpression of MLK3) in CHO cells; elicits neuroprotective and anti-inflammatory responses in models of neurodegenerative diseases.




M-443 (M443;M 443) is a specific, irreversible inhibitor of MLK-related kinase MRK (ZAK), does not inhibit Bcr-Abl; effectively inhibits MRK downstream signals in primary medulloblastoma cells and prevents cell-cycle arrest induced by IR; also inhibits radiation-induced activation of both p38 and Chk2; achieves a synergistic increase in survival in an animal model of medulloblastoma.

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