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CAL-101 (Idelalisib, GS-1101), is a p110δ selective phosphatidylinositol-3-kinase inhibitor in a kinome-wide screen using purified enzymes and in cell-based PI3K isoform-specific assays. Phosphatidylinositol-3-kinase p110δ serves as a central integration point for signaling from cell surface receptors known to promote malignant B-cell proliferation and survival. CAL-101 can block constitutive phosphatidylinositol-3-kinase signaling, resulting in reduced phosphorylation of Akt and other downstream effect factors, an increase in poly(ADP-ribose) polymerase and caspase cleavage and an induction of apoptosis. These effects have been observed across a broad range of immature and mature B-cell malignancies. In addition, CAL-101 abrogated protection from spontaneous apoptosis induced by B cell–activating factors CD40L, TNF-α, and fibronectin.

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