mlk3

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).

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.

DMX-5804 is a potent, selective MAP4K4 inhibitor, with an IC50 of 3 nM.DMX-5804 enhances cardiomyocyte survival, and reduces ischemia-reperfusion injury in mice.

Famlasertib is a potent inhibitor of the mitogen-activated protein kinase kinase kinase kinase (MAP4K) family, capable of penetrating the brain. It exhibits an IC50 value of 0.3 nM for HGK (MAP4K4) and 23.7 nM for MLK3.

CS640 is a selective calmodulin-dependent kinase inhibitor, targeting multiple isoforms, namely CaMK1D, CaMK1B, CaMK1A, CaMK1G, PIP5K1C, MEK5, RIPK4, and MLK3, with respective IC50 values of 0.08, 0.03, 0.001, 0.001, 11.2, 0.025, 5.69, and 2.75 μM. Additionally, CS640 exhibits inhibitory properties toward CYP450 enzymes 2C9 and 2C19 with IC50 values of 6 and 10 μM, correspondingly [1].

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].

CEP1347-VHL-02 is a PROTAC that selectively targets MLK3. This compound is composed of the target protein ligand CEP-1347, the E3 ubiquitin ligase ligand (S,R,S)-AHPC-Me, and the PROTAC linker Amino-PEG3-CH2COOH. The participating component responsible for controlling the target protein ligand activity is CEP-1347-acid, whereas the conjugate of the E3 ubiquitin ligase ligand and linker is identified as (S,R,S)-AHPC-Me-CO-CH2-PEG3-NH2.

Dehydroglyasperin D exhibits anticancer, anti-inflammatory, anti-obesity, antioxidant and anti-aldose reductase effects, it inhibits the proliferation of HT-29 human colorectal cancer cells through direct interaction with phosphatidylinositol 3-kinase; it also mediates suppression of both COX-2 expression and the MLK3 signalling pathway through direct binding and inhibition of MLK3. Dehydroglyasperin D shows strong ferric reducing activities and effectively scavenged DPPH, ABTS(+), and singlet oxygen radicals.