URMC-099
Mixed-lineage kinase 3 inhibitor / URMC-099 is a potent (IC50 = 14 nM), brain penetrant mixed-lineage kinase 3 inhibitor (MLK3). It also potently inhibits FLT3 (4 nM in vitro, but 560 nM in vivo), LRRK2 (11 nM), and ABL1 (3 nM).1 URMC-099 displayed neuroprotective effects in HIV-associated neurocognitive disorders2 and facilitated microglial amyloid- degradation and clearance in mouse models.3,4 URMC-099 increased CD8+ T cells in mice and increased the CD8+GZMB+ T cell population in blood mononuclear cells isolated from breast cancer patients.5
Biochemicals & reagents
1229582-33-5
1) Goodfellow et al. (2013), Discovery, synthesis, and characterization of an orally bioavailable, brain penetrant inhibitor of mixed lineage kinase 3; J. Med. Chem. 56 8032 2) Marker et al. (2013), The new small-molecule mixed-lineage kinase 3 inhibitor URMC-099 is neuroprotective and anti-inflammatory in models of human immunodeficiency virus-associated neurocognitive disorders; J. Neurosc. 33 9998 3) Dong et al. (2016), The mixed-lineage kinase 3 inhibitor URMC-099 facilitates microglial amyloid-? degradation; J. Neuroinflammation 13 184 4) Kiyota et al. (2018), URMC-099 facilitates amyloid-? clearance in a murine model of Alzheimer's disease; J. Neuroinflammation 15 137 5) Kumar et al. (2020), Mixed lineage kinase 3 inhibition induces T cell activation and cytotoxicity; Proc. Natl. Acad. Sci. USA 9 34567
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TARGET: Kinase; Lysosome -- PATHWAY: Cytokine -- RESEARCH AREA: Neuroscience; Immunology; Vesicles -- DISEASE AREA: Neurodegeneration; InflammationInfectious Disease