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 found in hematolymphoid cells and mesancymal stem cells. K118 is a water soluble SHIP1 inhibitor which does not inhibit SHIP2. Treatment with K118 (10 mg/kg) on obese mice on a high fat diet resulted in reduced body mass and lowered fat content when compared to pre-treatment and non-treated control animals. The treated mice had reduced blood glucose and insulin levels in addition to improved glucose tolerance. K118 treatment also reduced the amount of age-related fat accumulation in mice.
