In vitro
CAL-101, as a PI3K-delta selective inhibitor, can potently inhibit p110delta with IC50 of 2.5 nM and EC50 of 8nM. CAL-101 blocked constitutive phosphatidylinositol-3-kinase signaling as constitutive phosphatidylinositol-3-kinase pathway activation is p110delta-dependent. And the inhibition of PI3K by CAL-101 decrease phosphorylation of Akt and other downstream effectors, an increase in poly(ADP-ribose) polymerase and caspase cleavage and an induction of apoptosis. For CLL, CAL-101 can promote apoptosis in primary CLL. CAL-101 cause cytotoxicity depend on caspase signaling. CAL-101 inhibits CLL cell chemotaxis toward CXCL12 and CXCL13 and migration beneath stromal cells (pseudoemperipolesis). CAL-101 also down-regulates secretion of chemokines in stromal cocultures and after BCR triggering. CAL-101 reduces survival signals derived from the BCR or from nurse-like cells, and inhibits BCR- and chemokine-receptor-induced AKT and MAP kinase (ERK) activation.
Download Datasheet