MLK

MLK-IN-1 is a potent and selective mixed-lineage kinase 3 (MLK-3) inhibitor, showing excellent brain penetration and high specificity for MLK-3. MLK-IN-1 at 100 nM supports sustained axonogenesis in cultures challenged with HIV-1 Tat-activated microglia and protects neuronal cells from Tat-induced damage, establishing it as a valuable probe for neuroinflammation and neurodegeneration research.

LY-364947 (HTS466284) is a potent ATP-competitive inhibitor of TGFβR-I.

MLK-IN-2 (Compound 9a), with its 3H-imidazole [4,5-b] pyridine structure, serves as a potent Mixed Lineage Kinase 3 (MLK3) inhibitor with an IC50 value of 6 nM. This compound is valuable for research in cancer and neurodegenerative diseases [1].

MLKL-IN-2 is an MLKL inhibitor with potential tumorigenic activity for the study of cellular necrosis-related diseases.

MLKL-IN-1, a covalent inhibitor of MLKL, has a dissociation constant (Kd) of 50 μM.

MLKL-IN-6 (compound P28) is a mixed lineage kinase inhibitor that specifically targets the Mixed Lineage Kinase domain-like (MLKL) protein. It effectively prevents MLKL phosphorylation and oligomerization, which are critical steps in cell necrosis. Additionally, MLKL-IN-6 restrains immune cell death, diminishes adhesion factor expression, exhibits low cytotoxicity, impedes hepatic stellate cell activation, decreases liver fibrosis marker levels, and exerts anti-fibrotic effects [1].

MLK3-IN-1 (Compound 37) is a selective inhibitor of mixed-lineage kinase 3 (MLK3) with an IC50 of less than 1 nM. It also inhibits FAK with an IC50 of 15.5 μM. In both murine and human liver microsomes, MLK3-IN-1 demonstrates excellent metabolic stability.

URMC-099 is an orally bioavailable, brain penetrant MLK inhibitor (IC50: 19/42/14/150 nM, for MLK1/MLK2/MLK3/DLK), and also inhibits LRRK2 activity (IC50: 11 nM).

GW806742X is an inhibitor of Mixed Lineage Kinase Domain-Like protein (MLKL) which binds the MLKL pseudokinase domain (Kd: 9.3 μM) with anti-necroptosis activity. GW806742X has activity against VEGFR2.

AZ7550, an active metabolite of AZD9291, inhibits the activity of IGF1R (IC50: 1.6 μM).

M443 is a potent small molecule inhibitor of MRK that inhibits radiation-induced activation of p38 and Chk2 and can be used in cancer research.

TC13172 is a potent and covalent inhibitor that specifically targets the mixed lineage kinase domain-like protein (MLKL), exhibiting significant selectivity for MLKL over the closely related receptor-interacting serine/threonine kinase 1 (RIPK1) and RIPK3 at a concentration of 10 µM.TC13172 effectively inhibits necroptosis induced by the TSZ combination (TNF-α, a Smac mimetic, and Z-VAD-FMK) in HT-29 cells with a EC50 of 2 nM and, at 100 nM, blocks TSZ-induced oligomerization and plasma membrane translocation of MLKL.

NecroX-2 is a cell-permeable necrosis inhibitor with antioxidant properties. NecroX-2 selectively suppresses necrotic cell death triggered by oxidative stress. NecroX-2 does not confer protection against apoptosis induced by staurosporine or etoposide but shows protective effects under conditions such as cold shock, hypoxia, and oxidative stress in vitro.

IM-54 is a cell-permeable, effective, and selective necrosis inhibitor.

P505-15 Acetate is a selective inhibitor of spleen tyrosine kinase that acts by suppressing leukocyte immune function and inflammation and leading to a reduction in arthritis score and attenuated histological damage.

PRT062607 hydrochloride (P505-15 Hydrochloride) is a selective inhibitor of Syk (IC50: 1 nM). It displays at least 80-fold selectivity for Syk over other kinases.

Ligustroflavone (Nuezhenoside) has anti-inflammatory activity.

Aurantiamide has anti-cancer, anti-inflammatory and antinociceptive activities, it may suppress the growth of malignant gliomas by blocking autophagic flux.Aurantiamide has an anti-neuroinflammatory effect on LPS stimulation through its inhibition of the

Cerdulatinib hydrochloride (PRT2070 hydrochloride) is an oral active, multi-targeted tyrosine kinase inhibitor with IC50 of 12 nM/6 nM/8 nM/0.5 nM and 32 nM for JAK1/JAK2/JAK3/TYK2 and Syk, respectively. Also inhibits 19 other tested kinases with IC50 less than 200 nM.

Necrosulfonamide ((E)-Necrosulfonamide) is a necroptosis inhibitor that targets MLKL and is selective. Necrosulfonamide prevents the MLKL-RIP1-RIP3 necrosomal complex from interacting with its downstream effectors.

SZM-1209 is a potent and specific RIPK1 inhibitor with oral activity, displaying a dissociation constant (Kd) of 85 nM. It demonstrates substantial anti-necroptotic efficacy with an EC50 of 22.4 ± 8.1 nM and possesses therapeutic effects against systemic inflammatory response syndrome (SIRS) and acute lung injury (ALI) [1].

NecroIr1, an iridium(III) complex, acts as a necroptosis inducer in Cisplatin-resistant lung cancer cells (A549R). It selectively targets mitochondria, causing oxidative stress and reducing mitochondrial membrane potential (MMP). By activating receptor-interacting serine-threonine kinase 3 (RIPK3) and Mixed Lineage Kinase (MLKL), and modulating CDK4 expression, NecroIr1 facilitates cell death mechanisms [1].

NecroIr2, an iridium(III) complex, functions as a necroptosis inducer in cisplatin-resistant lung cancer cells (A549R). It preferentially accumulates in mitochondria, causing oxidative stress and a reduction in mitochondrial membrane potential (MMP). Moreover, NecroIr2 initiates the activation of receptor-interacting serine/threonine kinase 3 (RIPK3) and mixed lineage kinase domain-like pseudokinase (MLKL), while also regulating CDK4 expression [1].

RIPK3-IN-3 (compound 20) is a selective RIPK3 inhibitor with a potent IC50 value of 10 nM, effectively blocking RIPK3-mediated phosphorylation of MLKL, preventing oligomerization and necroptosis induction. Moreover, RIPK3-IN-3 suppresses CXCL5 secretion and impedes AsPC-1 cell migration and invasion [1].