IPI-549 (1693758-51-8) is a potent and highly selective inhibitor of PI3K-γ in both biochemical (IC50?= 16 nM) and cellular (IC50?= 12.2 nM) assays.1?Macrophage PI3K-γ 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-γ 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
IPI-549 is a selective phosphoinositide-3-kinase (PI3Kγ) Inhibitor. PI3Kγ inhibitors can be used to develop potential treatment for inflammatory and autoimmune diseases.
1) Evans?et al.?(2016)?Discovery of a Selective Phosphoinositide-3-Kinase (PI3K)-gamma Inhibitor (IPI-549) as an Immuno-Oncology Clinical Candidate; ACS Med. Chem. Lett.?7?862
2) Kaneda?et al.?(2016)?PI3Kγ is a molecular switch that controls immune suppression; Nature?539?437
3) De Henau?et al.?(2016);?Overcoming resistance to checkpoint blockade therapy by targeting PI3Kγ in myeloid cells; Nature?539?443
4) De Vera?et al. (2019);?Immuno-oncology agent IPI-549 is a modulator of P-glycoprotein (P-gp, MDR1, ABCB1)-mediated multidrug resistance (MDR) in cancer: In vitro and in vivo; Cancer Letters?442?91
