MLi-2

MLi-2 is an orally active and highly selective LRRK2 inhibitor with an IC₅₀ of 0.76 nM. MLi-2 has the potential for Parkinson’s disease^[1]. IC50 & Target: IC50: 0.76 nM (LRRK2)^[1] In Vitro: MLi-2 exhibits exceptional potency in a purified LRRK2 kinase assay in vitro( IC₅₀=0.76 nM), a cellular assay monitoring dephosphorylation of LRRK2 pSer935 LRRK2 (IC₅₀=1.4 nM), and a radioligand competition binding assay (IC₅₀=3.4 nM). MLi-2 has greater than 295-fold selectivity for over 300 kinases in addition to a diverse panel of receptors and ion channels^[1]. In Vivo: Acute oral and subchronic dosing in MLi-2 mice results in dose-dependent central and peripheral target inhibition over a 24-hour period as measured by dephosphorylation of pSer935 LRRK2. Treatment of MitoPark mice with MLi-2 is well tolerated over a 15-week period at brain and plasma exposures. Morphologic changes in the lung, consistent with enlarged type II pneumocytes, are observed in MLi-2-treated MitoPark mice^[1].