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Endocrine/metabolic disease


Hypoxia-inducible factor prolyl hydroxylase 3 (EGLN3; HIF-PH3; PHD3)

Mouse studies suggest liver-specific inhibition of PHD3 could help treat type 2 diabetes without the toxicity of pan-PHD inhibition. In mice fed a high-fat diet, liver-specific knockout of Phd3 improved insulin sensitivity and reversed the diabetic phenotype compared with wild-type Phd3 expression. In the Phd3-deficient mice, liver-specific knockout of Phd1 (Egln2; Hif-ph1) and Phd2 (Egln1; Hif-ph2) did not yield additional metabolic improvements but caused hepatic steatosis. Next steps include identifying a PHD3-specific inhibitor and evaluating it in additional animal models.

SciBX 6(40); doi:10.1038/scibx.2013.1126
Published online Oct. 17, 2013

Unpatented; licensing status not applicable

Taniguchi, C.M. et al. Nat. Med.; published online Sept. 15, 2013;
Contact: Amato J. Giaccia, Stanford University, Stanford, Calif.