| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2530124 | Current Opinion in Pharmacology | 2012 | 8 Pages |
PI3K is critical for the normal function of the immune system, however dysregulated PI3K mediated signaling has been linked to the development of many immune mediated pathologies. This review describes current progress in the development of isoform-specific PI3K inhibitors that hold promise for the treatment of hematopoietic malignancies as well as for inflammatory and autoimmune diseases. A SH2-domain containing inositol-5-phosphatase (SHIP) is a regulator of PI3K signaling, and is also discussed as a potential drug target for immunomodulation and the treatment of leukemia. Recent progress has been made in the development of small molecule compounds that potently and selectively modulate SHIP activity and hence provide a novel mechanism to alter PI3K mediated signaling.
► PI3Kδ and PI3Kγ have non-redundant and often co-ordinated roles in immune cell function. ► Increasing appreciation of a role for PI3Kβ in the immune system. ► Inhibitors of PI3Kδ isoform have proven successful for treatment of B cell malignancies. ► The lipid phosphatase SHIP-1 offers a novel opportunity to manipulate PI3K-dependent signaling in the immune system. ► Both small molecule activators and inhibitors of SHIP-1 have been reported and show efficacy as anti-leukemic drugs.
