CZC-25146 hydrochloride

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

CZC-25146 是一种选择性 LRRK2 抑制剂，对野生型 LRRK2 和 G2019S LRRK2 的 IC50 分别为 4.76 nM/6.87 nM。

CZC-25146 is a selective LRRK2 inhibitor with IC50 of 4.76 nM/6.87 nM for wild type LRRK2 and G2019S LRRK2 respectively.

CZC-25146 (0.01-5 μM; 7 days) does not cause cytotoxicity in human cortical neurons, nor blocking neuronal development.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.CZC-25146 (0.06-1000 nM) rescues LRRK2 G2019S-induced neurite defects in primary human neurons in a dose-dependent manner.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. Cell Cytotoxicity Assay Cell Line:Human cortical neurons Concentration:0.01, 0.1, 1 and 5 μM Incubation Time:7 days Result:Did not cause cytotoxicity in human cortical neurons at concentrations below 5 μM over a seven-day treatment in culture, nor did it block neuronal development.

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.CZC-25146 (250 mg/kg; p.o.; 14 days) reduces the ATZ polymer levels in over expressing human polymeric ATZ mice. Animal Model:Male CD-1 mice Dosage:1 mg/kg for i.v.; 5 mg/kg for p.o.Administration:i.v. and p.o.; single dosage Result:Pharmacokinetic Parameters of CZC-25146 in male CD-1 mice.Animal Model:Genetically modified male mice (6 weeks; over expressing human polymeric ATZ) Dosage:250 mg/kg Administration:p.o.; 14 days Result:Dramatically and reproducibly reduced the ATZ polymer levels with an overall reduction from 60% in the control group to 37%

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Autophagy

LRRK2

LRRK2 (G2019S) LRRK2 (WT)

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1330003-04-7

525

C22H26ClFN6O4S

>98% (HPLC)

DMSO: 15 mg/mL

Cl.COc1cc(ccc1Nc1ncc(F)c(Nc2ccccc2NS(C)(=O)=O)n1)N1CCOCC1

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(-20℃)

With Ice Pack

≥ 2 years