Duvelisib (IPI-145)

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Mechanism of action

From NCI Drug Dictionary: An orally bioavailable, highly selective and potent small molecule inhibitor of the delta and gamma isoforms of phosphoinositide-3 kinase (PI3K) with potential immunomodulating and antineoplastic activities. Upon administration, PI3K delta/gamma inhibitor IPI 145 prevents the activation of the PI3K delta/gamma-mediated signaling pathways which may lead to a reduction in cellular proliferation in PI3K delta/gamma-expressing tumor cells. Unlike other isoforms of PI3K, the delta and gamma isoforms are overexpressed primarily in hematologic malignancies and inflammatory and autoimmune diseases. By selectively targeting these PI3K isoforms, PI3K signaling in normal, non-neoplastic cells is minimally or not affected which would result in a more favorable side effect profile.

Preliminary data

Chronic lymphocytic leukemia

  1. Abstract: Manish Patel, Brad S. Kahl, Steven M. Horwitz, Francine M. Foss, Yasuhiro Oki, Pierluigi Porcu, Jennifer Sweeney, Kerstin Allen, Kerrie Faia, Patricia Harris, Joi Dunbar, Howard M. Stern, Patrick Kelly, Susan O'Brien. Preliminary Safety and Efficacy Of IPI-145, a Potent Inhibitor Of Phosphoinositide-3-Kinase-δ,γ, In Patients With Chronic Lymphocytic Leukemia. Blood Nov 2013,122(21)677 link to original abstract