IPI-549 is a potent and highly selective inhibitor of PI3K- in both biochemical (IC50 = 16 nM) and cellular (IC50 = 12.2 nM) assays.1 Macrophage PI3K- has been found to be a critical switch between immune stimulation and suppression.2 IPI-549 has been used to reshape tumor immune microenvironments and promote cytotoxic T-cell-mediated tumor regression. Resistance to immune checkpoint blockade in 4T1 and B16-GMCSF tumors was overcome when anti-PD-1 or anti-CTLA4 therapies were combined with PI3K inhibition via IPI-549.3 IPI-549 mono-treatment also resulted in tumor growth inhibition in several cancer cell lines.3 IPI-549 has also been shown to modulate P-glycoprotein-mediated multidrug resistance.4
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