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Heme oxygenase inhibitors and inducers act on the enzymes that break down heme into biliverdin. The reaction also releases iron and carbon monoxide, and biliverdin is then reduced to bilirubin. In 1968 microsomal heme oxygenase was shown to convert heme to bilirubin enzymatically. In 1986 two forms of the enzyme were distinguished in rat liver, and only one of them, heme oxygenase 1 (HO-1), was inducible. Tin mesoporphyrin and zinc protoporphyrin are metalloporphyrins that compete with heme for the enzyme. HO-1-IN-1 is a further HO-1 inhibitor, whereas hemin and coniferaldehyde induce HO-1 expression in cells.
Synonyms: Zn(II)-protoporphyrin IX; ZnPP; Zinc Protoporphyrin-9
Zinc Protoporphyrin (Zn(II)-protoporphyrin IX) is a competitive heme oxygenase-1 (HO-1) inhibitor, markedly attenuates the protective effects of Phloroglucinol (PG) against H2O2.
HO-1-IN-1 (Compound 2) is a heme oxygenase 1 (HO-1) inhibitor with an IC50 of 250 nM.
Synonyms: Stannsoporfin
Tin(IV) mesoporphyrin IX dichloride (Stannsoporfin) is a heme oxygenase (HO) inhibitor being developed for the prevention of hyperbilirubinemia in infants at risk of developing jaundice, extracted from patent WO2011103196A1.
HO-1-IN-1 hydrochloride (Compound 2) is a heme oxygenase 1 (HO-1) inhibitor with an IC50 of 250 nM.
Sappanone A is an orally active homoisoflavone isolated from Caesalpinia sappan L., exhibiting notable anti-inflammatory and antioxidant properties. It functions as an inhibitor of phosphodiesterase 4 (PDE4) and NF-κB, key regulators of inflammatory signaling. Additionally, Sappanone A activates the Nrf2 pathway, leading to increased expression of the cytoprotective enzyme heme oxygenase-1 (HO-1). Sappanone A also inhibits RANKL-induced osteoclastogenesis, suggesting potential benefits in bone metabolism disorders. With its multifaceted bioactivity, Sappanone A holds significant promise for research in inflammation-related diseases, cardiovascular conditions, and bone health.
Synonyms: Tin-protoporphyrin IX; Sn-Protoporphyrin; SnPPIX
Tin protoporphyrin IX dichloride (SnPPIX) is a potent inhibitor of heme oxygenase-1 (HO-1), an enzyme involved in cellular stress responses and tumor progression. SnPPIX has been shown to sensitize pancreatic ductal adenocarcinoma (PDAC) tumors to chemotherapy in mouse models, enhancing therapeutic efficacy and supporting its potential use as a chemosensitizing agent in cancer treatment.
YS-49 monohydrate is a selective angiotensin receptor inhibitor, primarily targeting the angiotensin II pathway. This compound effectively reduces angiotensin II-stimulated proliferation of vascular smooth muscle cells by inducing heme oxygenase-1, offering potential therapeutic insights for cardiovascular research. Additionally, as an isoquinoline alkaloid, YS-49 demonstrates significant positive inotropic effects through the activation of cardiac β-adrenoceptors, making it a valuable reagent for studies involving cardiac function and vascular biology.
CS47 is a reversible inhibitor of Thioredoxin reductase 1 (TrxR1). It activates stress-responsive pathways involving glutathione (GSH) and iron regulation, leading to GSH depletion, heightened heme oxygenase-1 (HO-1) expression, and intracellular iron overload, ultimately inducing ferroptosis in KRAS-independent lung cancer models. CS47 demonstrates significant anticancer activity while exhibiting low cytotoxicity towards normal lung fibroblasts, making it a valuable tool for studying cancer mechanisms and therapeutic strategies.
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OB-24 is a selective small-molecule inhibitor of heme oxygenase-1 (HO-1), demonstrating an IC50 of 1.9 μM for HO-1 with minimal effect on HO-2 (IC50 > 100 μM). This compound exhibits significant anti-tumor and anti-metastatic activities, making it valuable for research applications in various cancer models, including prostate cancer, melanoma, ovarian carcinoma, and lung metastasis. OB-24 may serve as an essential tool for understanding HO-1's role in tumor progression and metastasis.
Heme Oxygenase-2-IN-1 is a selective inhibitor of heme oxygenase-2 (HO-2), demonstrating an IC50 of 0.9 μM for HO-2 and 14.9 μM for HO-1. This compound is valuable in research applications focused on elucidating the role of HO-2 in various biological processes and potential therapeutic interventions. Its specificity for HO-2 makes it a useful tool for studying associated signaling pathways and related diseases.
(3S,4R)-ME-344 is a selective inhibitor of mitochondrial heme oxygenase 1 (HO-1) that functions by binding to and modifying the structure of HO-1. This enantiomer promotes the translocation of HO-1 from the rough endoplasmic reticulum to the mitochondria specifically in drug-sensitive cell lines such as H460 and SHP-77. By decreasing mitochondrial ATP production and inducing reactive oxygen species (ROS), it disrupts redox homeostasis and mitochondrial function. With its notable antitumor activity, (3S,4R)-ME-344 is a valuable compound for research in cancer, including studies focused on breast cancer.
PIISVYWK is a potent PPARγ inhibitor that also acts as an activator of heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2). This compound effectively modulates the HO-1/Nrf2 signaling pathway, contributing to the reduction of oxidative stress and inflammation, while also exhibiting anti-obesity properties. PIISVYWK is suitable for research applications focused on obesity and related metabolic disorders.
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Heme Oxygenase-1-IN-2 is a selective inhibitor of heme oxygenase-1, exhibiting an IC50 of 0.95 μM. This compound demonstrates significant antiproliferative activity in vitro, making it a valuable tool in the study of reactive oxygen species and their roles in cellular processes. Its application extends to research involving oxidative stress and potential therapeutic interventions in various diseases related to dysregulated oxidative pathways.
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Synonyms: 1,2-Diisonicotinoylhydrazine
N'-Isonicotinoylisonicotinohydrazide is a competitive inhibitor of heme oxygenase (HO), demonstrating an IC50 range of 5-30 μM. This compound significantly impedes iron release, thereby disrupting iron acquisition in bacteria. It exhibits selective inhibitory effects on HO enzymes from Pseudomonas aeruginosa and Neisseria meningitidis, making it a valuable tool for investigating multidrug-resistant Gram-negative bacterial infections.
Dehydrocurdione, a sesquiterpene derived from zedoary, acts as a heme oxygenase-1 (HO-1) inhibitor. It is known to induce the expression of HO-1 in RAW 264.7 macrophages through interaction with Keap1, leading to the translocation of Nrf2 and activation of the HO-1 E2 enhancer. Additionally, Dehydrocurdione demonstrates anti-inflammatory properties by suppressing lipopolysaccharide-induced nitric oxide release, marking its potential application in research related to inflammation and oxidative stress.
Synonyms: RS-21607
Azalanstat is an imidazole-dioxolane derivative that functions as a specific inhibitor of heme oxygenase-1 (HO-1) and heme oxygenase-2 (HO-2), with IC50 values of 5.5 µM and 24.5 µM, respectively. This compound is valuable for studying the roles of HO-1 and HO-2 in various biological processes, including inflammation and oxidative stress. Its inhibition properties make Azalanstat a useful tool in research focused on diseases where the modulation of heme oxygenase activity is relevant.
Synonyms: ZnMP
Zn(II) Mesoporphyrin IX is a potent inhibitor of heme oxygenase, particularly affecting the enzymatic activity in bone marrow. This compound demonstrates significant biological activity by inhibiting the growth of erythroid and myeloid progenitor cells, as well as blocking rhG-CSF-induced mobilization of these cells into peripheral blood. Zn(II) Mesoporphyrin IX is suitable for research applications involving hematopoietic regulation. However, its photochemical properties and potential toxicity to hematopoietic growth warrant careful consideration in experimental designs.
Cu(II) Protoporphyrin IX serves as a negative control for Zn(II) Protoporphyrin, which acts as an inhibitor of heme oxygenase. Heme oxygenase plays a significant role in various biological processes, including tumor cell resistance to chemotherapy, modulation of free radical formation, and management of inflammation. This reagent is valuable for studies investigating the pathways linked to vascular repair and the mechanistic understanding of heme oxygenase-related processes.
Heme Oxygenase-1-IN-3 is a selective inhibitor of heme oxygenase-1 (HO-1), characterized by a dissociation constant (Kd) of 141 nM. This compound is valuable for investigating the role of HO-1 in cancer progression and neurodegenerative diseases. Its specificity makes it an essential tool for researchers studying the mechanism of HO-1 and its implications in various pathological conditions.
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Keap1-Nrf2-IN-9 is a selective inhibitor of the Keap1-Nrf2 protein-protein interaction (PPI) with a reported IC50 of 0.575 μM. This compound enhances the expression of Nrf2 target genes, including heme oxygenase 1 (Hmox1), glutathione S-transferase P (GstP), and the modulatory and catalytic subunits of glutamate-cysteine ligase (Gclc and Gclm). Keap1-Nrf2-IN-9 exhibits low cytotoxicity in ARPE19 cells, making it a valuable tool for studies focused on oxidative stress and cellular defense mechanisms.
OB-24 free base is a selective inhibitor of heme oxygenase 1 (HO-1), demonstrating notable potential for targeting advanced prostate cancer. This compound effectively reduces protein carbonylation and diminishes the formation of reactive oxygen species in prostate cancer cells through its specific inhibition of HO-1 activity. In vitro studies reveal that OB-24 significantly impairs cell proliferation, while in vivo experiments show a marked reduction in tumor growth and metastasis to lymph nodes and lungs. Additionally, OB-24 displays enhanced efficacy when used in conjunction with Taxol, making it a valuable tool for cancer research.
Synonyms: RS-21607 dihydrochloride
Azalanstat dihydrochloride is an inhibitor of heme oxygenase and lanosterol 14α-demethylase, demonstrating selective inhibitory activity against HO-1 (IC50 = 5.5 µM) and HO-2 (IC50 = 24.5 µM). This compound has been shown to reduce the maturation rate of rat oocytes and increase oocyte degeneration, as well as partially inhibit progesterone production in preovulatory follicles in rats. Its usage is pertinent in studies focused on reproductive biology and the biochemical pathways involving heme oxygenase and steroidogenesis.
N,N-dimethyldithiocarbamate potassium is an inhibitor of the ubiquitin-activating enzyme E1, leading to a decrease in the levels of activated ubiquitinated E1 (ub-E1). This compound is known to elevate intracellular copper levels, enhance oxidative stress, raise protein carbonyl levels, and promote the expression of heme oxygenase-1 (HO-1). N,N-dimethyldithiocarbamate potassium is particularly relevant for research into neurodegenerative disorders, including Parkinson's disease, by elucidating the impact of ubiquitin pathways on cellular stress responses.
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