Information
CZ415 CZ415, a potent ATP-competitive mTOR inhibitor with very good cell permeability.
Targets
mTOR (Cell-free assay) 8.07(pIC50)
In vitro
CZ415 shows no genotoxic potential and has very good cell permeability. Treatment of CZ415 leads to inhibition of phosphorylation for downstream targets of mTORC1 and mTORC2(IC50=14.5 nM for pS6RP and IC50=14.8 nM for pAKT). The immunosuppressive effect of CZ415 is measured by detecting secreted IFNγ after 18 h in stimulated human whole blood, and the resulting IC50 was 226 nM. CZ415 shows no genotoxic potential. It is neither mutagenic in a bacterial mutation assay (Ames test) nor does it show genotoxicity in the mouse lymphoma assay (MLA), in either the presence or absence of rat-liver S9 mix.
In vivo
In vivo studies show that CZ415 has moderate clearance and good oral bioavailability. In an anti-CD3 mouse model CZ415 efficiently inhibits mTOR downstream signaling and, in a CIA mouse model, shows significant antiinflammatory effects. With its extraordinary selectivity, drug-like properties and proven efficacy CZ415 represents an ideal molecule for the pharmacological investigation of mTOR pathophysiological role in vivo.
Cell Research(from reference)
Cell lines：HEK294T17 cells
Concentrations：3 µM start, 8 points 1:3 dilution steps.
Incubation Time：2 h
F2412106