Idea that redox properties might be involved in menadione efficacy, we tested analogs such as 1,4-dimethoxy-2methylnaphthalene, pentafluoromenadione, monohalogenated naphthoquinones, -tetralone and 1,4-naphthoquinone. All of these compounds were inactive except for 1,4-naphthoquinone. Menadione activated full-length recombinant human heme oxygenase-2 (FL-hHO-2) as effectively as rat brain enzyme, but it did not activate rat spleen heme oxygenase. Conclusions: These observations are consistent PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28381880 with the idea that naphthoquinones such as menadione bind to a receptor in HO-2 and activate the Elbasvir site Enzyme through a mechanism that may involve redox properties. Keywords: Heme oxygenase, Enzyme activator, Menadione, Agonist, In vitro, Redox propertiesBackground Drug targets or drug receptors include a broad array of cellular entities that range from receptors for intercellular transmitters to ion channels to genetic macromolecules to enzymes. Examples of the latter include xanthine oxidase, aldehyde dehydrogenase, angiotensin converting enzyme and acetylcholinesterase for which allopurinol, disulfuram, enalaprilate and organophosphates, respectively, act as ligands. In their 2010 review, Zorn and Wells [1] highlight the observation that inhibition of enzyme function is the usual modus operandi of drug discovery programs that target specific enzymes; accordingly in all of the* Correspondence: [email protected] 1 Department of Biomedical Molecular Sciences, School of Medicine, Queen’s University, Kingston, ON K7L 3 N6, Canada Full list of author information is available at the end of the articleexamples given above the ligands inhibited the enzymes. The pursuit of small molecules that activate enzymes is much less common as is the number of therapeutic agents that increase the activity of enzyme molecules. In the realm of heme oxygenases (HO), much of the progress made toward understanding their functional roles has exploited animals that are genetically deficient in either HO-1 or HO-2, treatments that induce HO-1, or drugs that inhibit these enzymes [2,3]. Through utilization of these tools, we now appreciate that heme oxygenases and their products are involved in an interesting array of cellular activities. For example, considerable evidence revealed that HO-1 affords tissue protection in the vasculature due to the antioxidant, anti-inflammatory and anti-apoptotic properties of its products (see review by Araujo et al. [4]). Similarly,?2014 Vukomanovic et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Vukomanovic et al. Medical Gas Research 2014, 4:4 http://www.medicalgasresearch.com/content/4/1/Page 2 ofthere is substantial evidence that HO-1 protects neurons against oxidative stress [5]. The first generation of HO inhibitors comprises the metalloporphyrins, such as zinc protoporphyrin (ZnPP) and tin protoporphyrin (SnPP), which are powerful inhibitors of both HO-1 and HO-2 [6]. With respect to the cardiovascular system, Araujo et al. [4] have reviewed the evidence showing that HO-1 is protective against vasc.