Omipalisib, also known as GSK2126458, is a small-molecule pyridylsulfonamide inhibitor of phosphatidylinositol 3-kinase (PI3K) with potential antineoplastic activity. Omipalisib (GSK2126458, GSK458) is a highly selective and potent inhibitor of p110α/β/δ/γ, mTORC1/2 with Ki of 0.019 nM/0.13 nM/0.024 nM/0.06 nM and 0.18 nM/0.3 nM in cell-free assays, respectively. It is also a low picomolar inhibitor of the common activating mutants of p110a (E542K, E545K, and H1047R) found in human cancer. Omipalisib (GSK2126458) binds to and inhibits PI3K in the PI3K/mTOR signaling pathway, which may trigger the translocation of cytosolic Bax to the mitochondrial outer membrane, increasing mitochondrial membrane permeability and inducing apoptotic cell death. Bax is a member of the proapoptotic Bcl2 family of proteins. PI3K, often overexpressed in cancer cells, plays a crucial role in tumor cell regulation and survival. GlaxoSmithKline (GSK) is developing omipalisib, a phosphoinositide 3-kinase/mammalian target of rapamycin (PI3K/mTOR) inhibitor as well as mTOR complex 1 and 2 inhibitor, for the potential oral treatment of cancer and idiopathic pulmonary fibrosis.