Duvelisib (Mechanism of Action)

In this article, we will discuss Duvelisib (Mechanism of Action). So, let’s get started.

Mechanism of Action

Duvelisib is an inhibitor of PI3K with inhibitory activity predominantly against PI3K-δ and PI3K-γ isoforms expressed in normal and malignant B-cells. Duvelisib induced growth inhibition and reduced viability in cell lines derived from malignant B-cells and in primary CLL tumor cells. Duvelisib inhibits several key cell-signaling pathways, including B-cell receptor signaling and CXCR12-mediated chemotaxis of malignant B-cells. Additionally, duvelisib inhibits CXCL12-induced T cell migration and M-CSF and IL-4 driven M2 polarization of macrophages.

Pharmacodynamics

At the recommended dose of 25 mg BID, reductions in levels of phosphorylated AKT (a downstream marker for PI3K inhibition) were observed in patients treated with Duvelisib.

Cardiac Electrophysiology
The effect of multiple doses of Duvelisib 25 and 75 mg BID on the QTc interval was
evaluated in patients with previously treated hematologic malignancies. Increases of > 20 ms in the QTc interval were not observed.

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