CZC-25146 (hydrochloride)

CZC-25146 hydrochloride is a potent LRRK2 inhibitor with IC₅₀ values of 4.76 nM and 6.87 nM for wild-type LRRK2 and G2019S LRRK2, respectively. CZC-25146 hydrochloride inhibits PLK4, GAK, TNK1, CAMKK2 and PIP4K2C as well. CZC-25146 hydrochloride prevents mutant LRRK2-induced injury of neurons in vitro. CZC-25146 hydrochloride exhibits relatively favorable pharmacokinetic properties in mice. CZC-25146 hydrochloride can increase normal α-1-antitrypsin (AAT) secretion and reduce inflammatory cytokines. CZC-25146 hydrochloride can be used to research Parkinson's disease and liver diseases^[1][2][3]. IC50 & Target: IC₅₀: 4.76 nM (wild-type LRRK2), 6.87 nM (G2019S LRRK2)^[1] In Vitro: CZC-25146 (0.01-5 μM; 7 days) does not cause cytotoxicity in human cortical neurons, nor blocking neuronal development^[1].
CZC-25146 (0.01-5 μM; 2 days) potently attenuates G2019S LRRK2-mediated toxicity in primary rodent neurons in a concentration-dependent manner with an EC₅₀ of ~100 nM^[1].
CZC-25146 (0.06-1000 nM) rescues LRRK2 G2019S-induced neurite defects in primary human neurons in a dose-dependent manner^[1].
CZC-25146 (14.3 and 28.6 μM; 48 h) markedly reduces The mutant AAT encoded by the Z allele (ATZ) polymer load and restores AAT secretion in iPSC-Hepatocyte, without compromising cell viability^[3]. In Vivo: CZC-25146 (1 mg/kg for i.v.; 5 mg/kg for p.o.; single dosage) exhibits relatively good pharmacokinetic properties and an extensive distribution throughout animal body following intravenous injection into mice^[1].
CZC-25146 (250 mg/kg; p.o.; 14 days) reduces the ATZ polymer levels in over expressing human polymeric ATZ mice^[3].