Indication

Target/marker/pathway

Summary

Licensing status

Publication and contact information

Other

Poisoning

Hypoxia-inducible factor prolyl hydroxylase 1 (EGLN2; HIF-PH1; PHD1); PHD2 (EGLN1; HIF-PH2); PHD3 (EGLN3; HIF-PH3)

Mouse studies suggest pan-PHD inhibitors could help prevent damage to the GI tract and death resulting from acute radiation exposure. In irradiated mice, knockout of Phd1, Phd2 and Phd3 in GI tissues or pretreatment with a pan-PHD inhibitor decreased markers of GI toxicity and increased survival compared with no knockout or with vehicle pretreatment. In wild-type mice, the pan-PHD inhibitor improved survival in animals treated after total abdominal irradiation but failed to do so in animals treated after total body irradiation. Ongoing work includes testing additional PHD inhibitors in mice before and after radiation exposure.
FibroGen Inc., Astellas Pharma Inc. and AstraZeneca plc have the small molecule PHD inhibitor roxadustat (FG-4592; ASP1517) in Phase III testing to treat anemia in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD).
FibroGen and Astellas have the small molecule PHD inhibitor FG-2216 (YM311) in Phase II testing to treat anemia in patients with CKD.
Akebia Therapeutics Inc. has the oral PHD inhibitor AKB-6548 in Phase IIb testing to treat anemia in patients with CKD.

SciBX 7(24); doi:10.1038/scibx.2014.719
Published online June 19, 2014

Patent application filed; available for licensing

Taniguchi, C.M. et al. Sci. Transl. Med.;
published online May 14, 2014;
doi:10.1126/scitranslmed.3008523
Contact: Amato J. Giaccia, Stanford University, Stanford, Calif.
e-mail:
giaccia@stanford.edu