CZ415 is a highly selective potent mTOR inhibitor with little activity on other lipid and protein kinases with efficacy in a collagen induced arthritis model and exhibits excellent cell permeability. In the issue, Bergamini et al., who has identified CZ415, confirmed with its extraordinary selectivity, drug-like properties and proven efficacy in vivo, CZ415 represents an ideal molecule for the pharmacological investigation of mTOR pathophysiological role in vivo. Assessed in dose response format from HEK293T cells after treatment with CZ415: 1. inhibition of S6RP (downstream of mTORC1) phosphorylation in HEK293T: IC50 = 14.5 nM; 2. inhibition of Akt (mTORC2 substrate) phosphorylation in HEK293T: IC50 = 14.8 nM; 3. inhibition of IFNγ release in stimulated human whole blood: IC50 = 226 nM
