SH2-Domain containing inositol 5-phosphatases (SHIP1 & SHIP2) dephosphorylate the 5-position of PI(3,4,5)P3 generating PI(3,4)P2. SHIP2 is ubiquitously expressed while SHIP1 is only found in hematopoietic lineage cells. 3AC is a selective inhibitor of SHIP1 (EC50 = 10 μM) and shows no inhibition of the other isoform, SHIP2, at concentrations up to 1 mM. 3AC promotes apoptosis of SHIP1-expressing leukemia cells (KG-1) and multiple myeloma cells (OPM) suggesting SHIP1 inhibition is a potential drug target for blood cancers. Mice treated with 3AC show increased numbers of MIR cells in the spleen and lymph nodes and increased numbers of granulocytes.
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