Heme oxygenase-1 and -2 (HO-1 and HO-2) are isoenzymes that catalyze the breakdown of exogenous heme to equimolar amounts of biliverdin, CO, and Fe2+ (Rahman et al. 2012). Mouse heme oxygenase knockout models show approximately 95% embryonic lethality (Poss and Tonegawa 1997). Study of HO activity has been impeded by the lack of specific HO inhibitors, with inhibition relying on metalloporphyrins that act as competitive antagonists for heme binding (Rahman et al. 2012). These inhibitors are non-specific and interfere with various other heme-binding proteins. QC-308 is a novel HO inhibitor that has an IC50 of 0.27 +/- 0.07 µM and is specific to the HO enzymes, though is not isoselective. QC-308 exhibits approximately 15-fold greater inhibition than the next best HO inhibitor (QC-65) due to the insertion of an additional phenyl group that associates with a previously uncharacterized hydrophobic pocket in the HO enzymes (Rahman et al. 2012).

References:

Konradsen, L. and E. Nexo (1988). "Epidermal growth factor in plasma, serum and urine before and after prolonged exercise." Regul Pept 21(3-4): 197-203. (Abstract) (http://www.ncbi.nlm.nih.gov/pubmed/3261875)

Poss, K. D. and S. Tonegawa (1997). "Heme oxygenase 1 is required for mammalian iron reutilization." Proc Natl Acad Sci U S A 94(20): 10919-10924. (Abstract) (http://www.ncbi.nlm.nih.gov/pubmed/9380735)

Rahman, M. N., D. Vukomanovic, J. Z. Vlahakis, W. A. Szarek, K. Nakatsu and Z. Jia (2012). "Structural insights into human heme oxygenase-1 inhibition by potent and selective azole-based compounds." J R Soc Interface. (Abstract) (http://www.ncbi.nlm.nih.gov/pubmed/23097500)