Background:

SF1670 is a potent and specific inhibitor of PTEN [1].

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a phosphatidylinositol 3’-phosphatase that converts PtdIns(3,4,5)P3 to phosphatidylinositol 4,5-bisphosphate. PTEN functions as a tumor suppressor that is mutated in many cancers [1].

SF1670 is a potent and specific PTEN inhibitor. SF1670 bound to the active site of PTEN and increased PtdIns(3,4,5)P3 signaling in neutrophils. In human neutrophils, SF1670 significantly increased Akt phosphorylation stimulated by chemoattractant and specifically increased PtdIns(3,4,5)P3 signaling. SF1670 efficiently increased Akt phosphorylation at the concentration of 250nM. In mouse neutrophils, SF1670 also increased Akt phosphorylation and PtdIns(3,4,5)P3 signaling, which was mediated by the inhibition of PTEN activity. In neutrophils, SF1670 significantly increased reactive oxygen species (ROS) production induced by fMLP. Also, SF1670 increased neutrophil polarization induced by fMLP, which was necessary for the chemotactic migration and neutrophil recruitment to sites of inflammation [1].

In a mouse neutropenia-associated bacterial pneumonia model, SF1670 increased the bacteria-killing capability and relieved inflammation-associated lung damage [1].

Reference:
[1].  Li Y, Prasad A, Jia Y, et al. Pretreatment with phosphatase and tensin homolog deleted on chromosome 10 (PTEN) inhibitor SF1670 augments the efficacy of granulocyte transfusion in a clinically relevant mouse model. Blood, 2011, 117(24): 6702-6713.