CZC-25146

SKU: orb1223397

Description

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.

Key Properties

• CAS Number: 1191911-26-8
• MW: 488.54
• Purity: >98% (HPLC)
• Formula: C₂₂H₂₅FN₆O₄S
• SMILES: COc1c(ccc(c1)N1CCOCC1)Nc1ncc(c(n1)Nc1ccccc1NS(=O)(=O)C)F
• Target: mTOR
• Solubility: DMSO : ≥ 46 mg/mL; 94.16 mM

Bioactivity

• In Vivo:
  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.
• In Vitro:
  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.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Quick Database Links

Gene Symbol

mTOR