Description
CL27c is a cell-permeable, inhaled lipophilic ester prodrug of CL27e, which is a potent, selective pan-class I PI3K inhibitor, CL27c is inactive in PI3K enzymatic assay, once inside the cytoplasm, CL27c is metabolized by unspecific esterases into CL27e; readily reduces Akt/PKB phosphorylation in chronic lymphocytic leukemia (CLL) cells stimulated with anti-IgM antibodies, as well as in murine neutrophils and bone marrow-derived macrophages (BMDM) stimulated with C5a; reduces insulin-evoked Akt phosphorylation in lungs, but no change in other tissues and no increase in blood glycaemia, in line with a local action; reduces inflammation and improves lung function in murine models of acute or glucocorticoid-resistant neutrophilic asthma