CZC-25146

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 是一种有效、特异性和代谢稳定的 LRRK2 抑制剂，对野生型 LRRK2（富含亮氨酸重复激酶-2）和 G2019S LRRK2 的 IC50 分别为 4.76/6.87 nM。

CZC-25146 is an effective, specific and metabolically stable LRRK2 inhibitor with IC50 of 4.76/6.87 nM for wild-type LRRK2(Leucine-rich repeat kinase-2) 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 (250 mg/kg; p.o.; 14 days) reduces the ATZ polymer levels in over expressing human polymeric ATZ mice.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. 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%.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.

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PI3K/Akt/mTOR signaling

mTOR

G2019S LRRK2| LRRK2

Neurological Disease

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1191911-26-8

488.54

C22H25FN6O4S

>98% (HPLC)

DMSO : ≥ 46 mg/mL; 94.16 mM

COc1c(ccc(c1)N1CCOCC1)Nc1ncc(c(n1)Nc1ccccc1NS(=O)(=O)C)F

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(-20℃)

With Ice Pack

≥ 2 years