Duvelisib: a phosphoinositide-3 kinase delta/gamma inhibitor for chronic lymphocytic leukemia.

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Vangapandu HV, Jain N, Gandhi V

Duvelisib: a phosphoinositide-3 kinase delta/gamma inhibitor for chronic lymphocytic leukemia.

Expert Opin Investig Drugs. 2017 May;26(5):625-632. doi: 10.1080/13543784.2017.1312338. Epub 2017 Apr 13.

PubMed ID

28388280 [ View in PubMed

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Abstract

INTRODUCTION: Frontline chemotherapy is successful against chronic lymphocytic leukemia (CLL), but results in untoward toxicity. Further, prognostic factors, cytogenetic anomalies, and compensatory cellular signaling lead to therapy resistance or disease relapse. Therefore, for the past few years, development of targeted therapies is on the rise. PI3K is a major player in the B-cell receptor (BCR) signaling axis, which is critical for the survival and maintenance of B cells. Duvelisib, a PI3K delta/gamma dual isoform specific inhibitor that induces apoptosis and reduces cytokine and chemokine levels in vitro, holds promise for CLL. Areas covered: Herein, we review PI3K isoforms and their inhibitors in general, and duvelisib in particular; examine literature on preclinical investigations, pharmacokinetics and clinical studies of duvelisib either as single agent or in combination, for patients with CLL and other lymphoid malignancies. Expert opinion: Duvelisib targets the PI3K delta isoform, which is necessary for cell proliferation and survival, and gamma isoform, which is critical for cytokine signaling and pro-inflammatory responses from the microenvironment. In phase I clinical trials, duvelisib as a single agent showed promise for CLL and other lymphoid malignancies. Phase II and III trials of duvelisib alone or in combination with other agents are ongoing.

DrugBank Data that Cites this Article

Drugs

Duvelisib

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Duvelisib	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform	Protein	Humans	Yes	Inhibitor	Details
Duvelisib	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform	Protein	Humans	Yes	Inhibitor	Details