Discovery Research
Further optimization of HIF-PHI for the treatment of anemia
FibroGen is engaged in research to optimize erythropoietic HIF-PHI and to further exploit certain beneficial properties resulting from the stabilization of HIF. Specific chemotypes have been further optimized to enhance the potency and selectivity of novel HIF-PHI in vitro and in vivo, focusing on their capacity to enhance iron utilization and to work optimally under conditions of anemia and hyporesponsiveness to erythropoiesis stimulating agents (ESAs), such as that which occurs in anemia of chronic disease. Other factors under optimization include improved dosing profiles and potential to reduce blood pressure.
Optimized, next generation HIF-PHI have been validated to selectively stimulate HIF-dependent erythropoietin secretion in vitro, and with intravenous or oral administration in vivo, to elevate circulating endogenous erythropoietin levels that are up to 1000-fold above levels in control groups.1
FibroGen expects to advance one or more of these compounds to the clinic in the near future.
References
1. Klaus, S., et al. (2008) Induction of Erythropoiesis in Rodents by Novel and Distinct Families of Orally Active HIF Prolyl Hydroxylase Inhibitors. Keystone Symposia Molecular, Cellular, Physiological and Pathogenic Responses of Hypoxia: Abstract 301.
