| Bioactivity | CZC-25146 is a potent and orally active LRRK2 inhibitor with IC50 values of 4.76 nM and 6.87 nM for wild-type LRRK2 and G2019S LRRK2, respectively. CZC-25146 inhibits PLK4, GAK, TNK1, CAMKK2 and PIP4K2C as well. CZC-25146 prevents mutant LRRK2-induced injury of neurons in vitro. CZC-25146 exhibits relatively favorable pharmacokinetic properties in mice. CZC-25146 can increase normal α-1-antitrypsin (AAT) secretion and reduce inflammatory cytokines. CZC-25146 can be used to research Parkinson's disease and liver diseases[1][2][3]. | ||||||||||||
| Target | IC50: 4.76 nM (wild-type LRRK2), 6.87 nM (G2019S LRRK2) | ||||||||||||
| Invitro | 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]. Cell Cytotoxicity Assay[1] Cell Line: | ||||||||||||
| In Vivo | CZC-25146 (250 mg/kg; p.o.; 14 days) reduces the ATZ polymer levels in over expressing human polymeric ATZ mice[3].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]. Animal Model: | ||||||||||||
| Name | CZC-25146 | ||||||||||||
| CAS | 1191911-26-8 | ||||||||||||
| Formula | C22H25FN6O4S | ||||||||||||
| Molar Mass | 488.54 | ||||||||||||
| Appearance | Solid | ||||||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | ||||||||||||
| Storage |
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| Reference | [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. [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. [3]. Deniz Kent, et al. Small molecule screen employing patient-derived iPS hepatocytes identifies LRRK2 as a novel therapeutic target for Alpha1 Antitrypsin Deficiency. |
CZC-25146
CAS: 1191911-26-8 F: C22H25FN6O4S W: 488.54
CZC-25146 is a potent and orally active LRRK2 inhibitor with IC50 values of 4.76 nM and 6.87 nM for wild-type LRRK2 and
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