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.
For research use only. We do not sell to patients.
- CAS No.: 1330003-04-7
- Formula: C22H26ClFN6O4S
- Molecular Weight:525.00
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
IC50: 4.76 nM (wild-type LRRK2), 6.87 nM (G2019S LRRK2)[1]
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].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Human cortical neurons
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Concentration:0.01, 0.1, 1 and 5 μM
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Incubation Time:7 days
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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[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Male CD-1 mice[1]
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Dosage:1 mg/kg for i.v.; 5 mg/kg for p.o.
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Administration:i.v. and p.o.; single dosage
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Result:Pharmacokinetic Parameters of CZC-25146 in male CD-1 mice[1].
i.v. (1 mg/kg) p.o. (5 mg/kg) CL (L/h/kg) 2.3 Vss (L/kg) 5.4 t1/2 (h) 1.6 1 tmax (h) 0 0.25 Cmax (ng/mL) 154 1357 AUClast (ng/mL·h) 419 2878 AUCinf (ng/mL·h) 434 2894 F (%) 133
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Animal Model:Genetically modified male mice (6 weeks; over expressing human polymeric ATZ)[3]
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Dosage:250 mg/kg
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Administration:p.o.; 14 days
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Result:Dramatically and reproducibly reduced the ATZ polymer levels with an overall reduction from 60% in the control group to 37%
Chemical Information
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CAS No. 1330003-04-7
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Molecular Weight 525.00
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Formula C22H26ClFN6O4S
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SMILES
CS(=O)(NC1=CC=CC=C1NC2=NC(NC3=CC=C(N4CCOCC4)C=C3OC)=NC=C2F)=O.Cl
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
[1]. Ramsden N, et al. Chemoproteomics-based design of potent LRRK2-selective lead compounds that attenuate Parkinson's disease-related toxicity in human neurons. ACS Chem Biol. 2011 Oct 21;6(10):1021-8. [Content Brief]
[2]. Atashrazm F, et al. LRRK2 inhibitors and their potential in the treatment of Parkinson's disease: current perspectives. Clin Pharmacol. 2016 Oct 20;8:177-189. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
CZC-25146 hydrochloride Related Classifications
HY-15800 Related Classifications
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