LRRK2-IN-23

LRRK2-IN-23 (compound 30) (preincubation 15 min; incubation 1 h) is a sub-nanomolar biochemical inhibitor of G2019S-LRRK2 (IC₅₀ < 0.2 nM), with an IC₅₀ = 0.3 nM against WT-LRRK2 in the LRRKtide phosphorylation assay and a WT/G2019S ratio > 1.5^[1].
LRRK2-IN-23 (0.25 μL compound in DMSO; incubated at 37 °C for 2 h) inhibits pS935-LRRK2 in HEK293 cells overexpressing WT or G2019S-LRRK2, with G2019S IC₅₀ = 1.1 nM, WT IC₅₀ = 145 nM, and 132-fold selectivity for the G2019S variant^[1].
LRRK2-IN-23 (1 μL test compound in 100% DMSO; incubated at 37 °C for 2 h) inhibits pS1292-LRRK2 autophosphorylation in HEK293 cells, with G2019S IC₅₀ = 1.0 nM and WT IC₅₀ = 33.7 nM, demonstrating 34-fold selectivity^[1].
LRRK2-IN-23 (3.75 μL test compound in 100% DMSO; incubation for 2 h; treatment at 65 °C for 10 min) inhibits phosphorylation at the endogenous Rab10 Thr73 site in HEK293 cells overexpressing WT or G2019S-LRRK2, with G2019S IC₅₀ = 4.7 nM, WT IC₅₀ = 473 nM, a selectivity of 101-fold, and pS935 immunoblot IC₅₀ values of 1.5 nM (G2019S) and 259 nM (WT), respectively^[1].