URMC-099 is a potent, orally bioavailable, brain penetrant inhibitor of mixed lineage kinase 3 (MLK3) with IC50 of 14 nM.
URMC-099 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).
URMC-099 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.
