产品
编 号：F121409
分子式：C22H26ClFN6O4S
分子量：525
分子式：C22H26ClFN6O4S
分子量：525
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CAS No: 1330003-04-7
产品详情
生物活性：
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.
体内研究：
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.i.v. (1 mg/kg) p.o. (5 mg/kg)
CL (L/h/kg)2.3
Vss (L/kg)5.4
t1/2 (h)1.61
tmax (h)00.25
Cmax (ng/mL)1541357
AUClast (ng/mL·h)4192878
AUCinf (ng/mL·h)4342894
F (%)133
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%
体外研究：
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.
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.
体内研究：
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.i.v. (1 mg/kg) p.o. (5 mg/kg)
CL (L/h/kg)2.3
Vss (L/kg)5.4
t1/2 (h)1.61
tmax (h)00.25
Cmax (ng/mL)1541357
AUClast (ng/mL·h)4192878
AUCinf (ng/mL·h)4342894
F (%)133
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%
体外研究：
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.
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