October 27 - November 1, 2004
American Society of Nephrology (ASN) Renal Week 2004, St. Louis, Missouri
Abstract PUB052

J Am Soc Nephrol 15: 773A

Stimulation of Erythropoiesis and Treatment of Anemia in Rodents by Oral Administration of FG-2216, a Novel HIF-Prolyl Hydroxylase Inhibitor. Qingjian Wang, G. Gou, V. Guenzler, T. Neff, S. Klaus, E. Turtle, C. J. Molineaux, D. A. Yeowell, A. Y. Lin. FibroGen,Inc., FibroGen,Inc., South San Francisco, CA.

Hypoxia has long been known to induce endogenous erythropoietin (EPO), which stimulates red blood cell production, resulting in enhanced oxygen delivery to tissues. Hypoxia-inducible factor (HIF) is a master transcriptional switch in regulating the hypoxic response in animals. Inhibitors of HIF prolyl hydroxylase (HIF-PH) stabilize HIF and mimic certain aspects of the hypoxic response, activating the transcription of a number of erythropoietic genes. FG-2216, a novel HIF-PH inhibitor that stabilizes HIF protein and stimulates EPO production is highly bioavailable in vivo after oral administration. Several studies in normal mice and rats show that FG-2216 elevates serum concentration of endogenous EPO, increases reticulocyte counts and raises hematocrit and hemoglobin in a dose-dependent and schedule-related fashion. Studies also demonstrate that FG-2216 prevents anemia associated with acute renal failure in a rat model of renal ischemia-reperfusion injury; corrects anemia associated with end-stage renal failure in a rat remnant kidney model; improves anemia induced in rats by the chemotherapeutic agent cisplatin; and accelerates recovery from phlebotomy-induced anemia in mice. Our results suggest a number of important clinical applications for this HIF-PH inhibitor to induce full erythropoiesis in treating anemic conditions ranging from kidney failure to anemia of chronic disease to cancer chemotherapy to surgical blood loss.

Scientific Advisor: FibroGen,Inc.

See also November 1, 2004 press release