N-(2-(2-(2-Methoxy-4-MorpholinophenylaMino)-5-fluoropyriMidin-4-ylaMino)phenyl)MethanesulfonaMide

Description

CZC-25146 is a potent inhibitor of leucine-rich repeat kinase 2 (LRRK2; IC₅₀ = 4.76 nM for the human recombinant kinase). It also inhibits LRRK2^G2019S, a mutant linked to neurotoxicity and Parkinson’s disease, with an IC₅₀ value of 6.87 nM. CZC-25146 is selective for LRRK2 over a panel of kinases in HeLa cell lysates, Jurkat/Ramos mixed cell lysates, as well as whole mouse brain extracts (IC₅₀s = >2 μM). It reduces LRRK2^G2019S-induced cell injury in rat primary cortical neurons.

Uses

CZC-25146 is a compound that acts as an inhibitor of LRRK2, a factor in the expression of Parkinsons’s disease, and is ATP-competitive.

storage

Store at -20°C

References

[1] ramsden n, perrin j, ren z, et al. chemoproteomics-based design of potent lrrk2-selective lead compounds that attenuate parkinson’s disease-related toxicity in human neurons. acs chemical biology, 2011, 6(10): 1021-1028.
[2] troxler t, greenidge p, zimmermann k, et al. discovery of novel indolinone-based, potent, selective and brain penetrant inhibitors of lrrk2. bioorganic & medicinal chemistry letters, 2013, 23(14): 4085-4090.