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Updated: Aug 9, 2026

Assessing Cellular Target Engagement by SHP2 (PTPN11) Phosphatase Inhibitors
Published on: July 17, 2020
Lipid phosphatases as drug discovery targets for type 2 diabetes
1Eli Lilly and Co., Endocrine Division, Lilly Research Laboratories, Indianapolis, Indianapolis 46285, USA. lazar_dan_f@lilly.com
Abstract:
The soaring incidence of type 2 diabetes has created pressure for new pharmaceutical strategies to treat this devastating disease. With much of the focus on overcoming insulin resistance, investigation has focused on finding ways to restore activation of the phosphatidylinositol 3'-kinase pathway, which is diminished in many patients with type 2 diabetes. Here we review the evidence that lipid phosphatases, specifically PTEN and SHIP2, attenuate this important insulin signalling pathway. Both in vivo and in vitro studies indicate their role in regulating whole-body energy metabolism, and possibly weight gain as well. The promise and challenges presented by this new class of drug discovery targets will also be discussed.
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