Heme Oxygenase (HO) Activator

Necrosulfonamide is a MLKL and Gasdermin D (GSDMD) inhibitor, capable of separately inhibiting necroptosis and pyroptosis of cells. Necrosulfonamide does not affect the activation of upstream signals, but specifically inhibits the downstream executor oligomerization step. Necrosulfonamide reduces the expression of the key kinases NLRP3 and caspase-1 involved in necroptosis and pyroptosis, activate the Nrf2 pathway and the downstream antioxidant enzymes, and also downregulates a variety of inflammatory factors. Necrosulfonamide plays significant roles in various diseases such as neurodegenerative diseases (such as Parkinson’s disease), tissue damage and ischemia-reperfusion injury, inflammatory bowel disease, osteoarthritis and fracture repair, and hair loss by regulating two important programmed necrosis pathways.

Gymnoside II is one of the main bioactive constituents isolated from Bletilla striata. Gymnoside II inhibits nano SiO₂-induced A549 cell viability reduction, apoptosis, and ROS generation by activating Nrf2. Gymnoside II upregulates HO-1 and γ-GCSc, while downregulating the Bax/Bcl-2 ratio. Gymnoside II is applicable for research on nano SiO₂-induced pulmonary injury.

FXR agonist 18 is an orally active FXR agonist, with an EC₅₀ of 10 nM against human FXR and an EC₅₀ of 1360 nM against human TGR5. FXR agonist 18 inhibits inflammatory responses by reducing nitrite production, downregulating the expression of pro-inflammatory genes (Tnf, Adgre1, Cyp8b1, upregulating the expression of FXR, Hmox1, Nqo1, Nrf2, and enhancing antioxidant responses. FXR agonist 18 ameliorates liver fibrosis in mice, exhibits protective effects in mice with cholestatic liver injury, and shows anti-MASH efficacy. FXR agonist 18 can be used in studies of metabolic dysfunction-associated steatohepatitis.

Nrf2/HO-1 activator 4 is a Nrf2/HO-1 activator. Nrf2/HO-1 activator 4 inhibits nitric oxide production and the expression of pro-inflammatory cytokines IL-1β, IL-6, TNF-α, as well as upstream inflammatory enzymes COX-2 and iNOS. Nrf2/HO-1 activator 4 reduces ROS accumulation, and restores GSH levels and SOD activity. Nrf2/HO-1 activator 4 ameliorates depression-like behaviors in mice. Nrf2/HO-1 activator 4 can be used for research on major depressive disorder.

Pulegone is a monoterpene ketone compound widely present in the essential oils of many plants. Pulegone can also be used as a bird repellent. Pulegone has multiple activities such as anti-inflammatory, antibacterial, antifungal, and anti-hyperalgesic effects. Pulegone is particularly effective against bacteria of the Salmonella species.

Epimedin A, one of the main flavonoid active components in Herba Epimedii, is orally active. Epimedin A can inhibit osteoclastogenesis, differentiation, and bone resorption. Epimedin A also possesses anti-inflammatory activity. Epimedin A can be used in the research of osteoporosis and inflammatory diseases.

Monotropein is an iridoid glycoside that can be isolated from the roots of Morinda officinalis. Monotropein inhibits the expression of inflammatory mediators in dextran sulfate sodium (DSS)-induced colitis mouse model. Monotropein exerts protective effects against IL-1β-induced apoptosis and catabolic responses on osteoarthritis chondrocytes. Monotropein has cartilage protective activity. Monotropein can alleviate Cisplatin (HY-17394)-induced acute kidney injury by inhibiting oxidative damage, inflammation and apoptosis through activation of Nrf2/HO-1 pathway and inhibition of NF-κB signaling. Monotropein can be studied in research for osteoarthritis, acute kidney injury and acute lung injury.

Perfluorohexane (AF-0150) is a perfluorocarbon. Perfluorohexane is also an enhancer of high-intensity focused ultrasound (HIFU) therapy. Perfluorohexane increases HO-1 and IL-10. Perfluorohexane exerts an antioxidant effect. Perfluorohexane alleviates lung injury induced by LPS (HY-D1056A1). Perfluorohexane improves the efficiency and precision of HIFU and reduces damage to surrounding normal tissues. Perfluorohexane can be used in the study of acute lung injury.

Carveol is an orally active monoterpenoid alcohol with neuroprotective, antioxidant, anti-inflammatory, anticonvulsant, antidiabetic, hypolipidemic and hepatoprotective activities. Carveol upregulates the expression of Bcl2, downregulates the expression of caspase-3, TNF-α, IL1β and IL6, activates the Nrf2/HO-1 antioxidant signaling pathway, inhibits the RAGE/NF-κB signaling pathway, and suppresses neuroinflammation and neuronal apoptosis. Carveol inhibits α-synuclein aggregation, improves cognitive ability, and inhibits α-amylase activity. Carveol exerts neuroprotective effects in a rat model of Parkinson's disease. Carveol exhibits antidiabetic effects in alloxan-induced diabetic rats. Carveol alleviates PTZ-induced seizures in rats. Carveol can be used in research related to Parkinson's disease, epilepsy, diabetes and ischemic stroke.

CYP2E1-IN-1 (Compound 10) is an orally active cytochrome P450 2E1 (CYP2E1) inhibitor with a K_d of 7.02 μM, an IC₅₀ of 1.64 μM, and a K_i of 0.897 μM. CYP2E1-IN-1 activates the Nrf2/HO-1 signaling pathway and inhibits ROS production, thereby alleviating pancreatic injury. CYP2E1-IN-1 has significant anti-inflammatory and antioxidant activities and can effectively reduce inflammation and oxidative stress in severe acute pancreatitis (SAP). CYP2E1-IN-1 can be used in the study of SAP and other inflammatory-related diseases.

zr17-2 is a cold inducible RNA-binding protein (CIRBP) agonist. zr17-2 has anti-inflammatory and anti-oxidant and can be used for the study of myocardial infarction. zr17-2 is a hypothermia mimetic molecule that reduces oxidative stress-induced retinal cell death.

6-Methoxyflavone is an orally active methoxyflavone. 6-Methoxyflavone suppresses neuroinflammation in microglia through the inhibition of TLR4/MyD88/p38 MAPK/NF-κB dependent pathways and the activation of HO-1/NQO-1 signaling. 6-Methoxyflavone induces S-phase arrest through the CCNA2/CDK2/p21CIP1 signaling pathway in HeLa cells. 6-Methoxyflavone inhibits NFAT Translocation into the nucleus and suppresses T cell activation. 6-Methoxyflavone partially restores chronic ethanol-induced behavioral deficits in mice. 6-Methoxyflavone antagonizes chronic constriction injury and diabetes associated neuropathic nociception expression. 6-Methoxyflavone can be used for the study of cancer, inflammation and neurological diseases.

Picein is an antioxidant and anti-inflammatory agent. Picein can be isolated from the leaves of Picrorhiza kurroa. Picein reduces MDA levels and increases the levels of SOD, GPX and TAC. Picein alleviates oxidative stress and promotes bone regeneration in osteoporotic bone defects by inhibiting Ferroptosis (via activation of the Nrf2/HO-1/GPX4 pathway). Picein prevents scopolamine (HY-N0296)-induced passive avoidance memory impairment in rats. Picein can be used in research related to osteoporotic bone defects and Alzheimer's disease.

PGK1-IN-1 (Compound 6e) is a potent and selective PGK1 inhibitor (IC₅₀: 33 nM). PGK1-IN-1 inhibits PGK1-mediated glycolytic metabolism and reduces glucose consumption/lactate production. PGK1-IN-1 enhances Nrf2 accumulation and HO-1 expression, and suppresses the transcription and protein levels of the inflammatory cytokines IL-1β and IL-6. PGK1-IN-1 ameliorates Dextran sulfate sodium (DSS) (HY-116282C)-induced experimental colitis in mice. PGK1-IN-1 can be used for research of inflammatory bowel disease (IBD).

2-tert-Butyl-1,4-benzoquinone is a food additive oxidant, an electrophilic metabolite of Butylated hydroxyanisole (HY-B1066), and an antibacterial agent. 2-tert-Butyl-1,4-benzoquinone reduces virulence factors, activates Nrf2, and induces S-arylation of its negative regulator Keap1. 2-tert-Butyl-1,4-benzoquinone induces HO-1. 2-tert-Butyl-1,4-benzoquinone exhibits quorum sensing inhibitory activity against Chromobacterium violaceum.

Erinacine C is the inhibitor for NF-κB signaling pathway and the activator for Nrf2 signaling pathway. Erinacine C exhibits antioxidant, neuroprotective and anti-inflammatory effects.

(E/Z)-Necrosulfonamide is a racemic compound of Necrosulfonamide (HY-100573). Necrosulfonamide is a MLKL and Gasdermin D (GSDMD) inhibitor, capable of separately inhibiting necroptosis and pyroptosis of cells. Necrosulfonamide does not affect the activation of upstream signals, but specifically inhibits the downstream executor oligomerization step. Necrosulfonamide reduces the expression of the key kinases NLRP3 and caspase-1 involved in necroptosis and pyroptosis, activate the Nrf2 pathway and the downstream antioxidant enzymes, and also downregulates a variety of inflammatory factors. Necrosulfonamide plays significant roles in various diseases such as neurodegenerative diseases (such as Parkinson’s disease), tissue damage and ischemia-reperfusion injury, inflammatory bowel disease, osteoarthritis and fracture repair, and hair loss by regulating two important programmed necrosis pathways.

Zinc (Zinc (II)) acetate, 99.99% trace metals basis is a heme oxygenase 1 (HO-1) activator and apoptosis inducer with cytotoxic and anticancer activities. Zinc acetate, 99.99% trace metals basis enhances HO-1 expression, alters the microRNA profile, and increases the level of caspase-cleaved cytokeratin 18. Zinc acetate, 99.99% trace metals basis also regulates the expression of Cdk2/cyclin E and interferes with cell cycle progression. Zinc acetate, 99.99% trace metals basis effectively inhibits cancer cell proliferation and induces their rapid death, with no significant cytotoxicity to non-tumor tissues. Zinc acetate, 99.99% trace metals basis has been widely used in studies related to hepatocellular carcinoma, prostate cancer, and other conditions.

Oleocanthal is an orally active phenolic seciridoid compound. Oleocanthal can be extracted from olive oil. Oleocanthal inhibits COX-1 and COX-2, reduces ROS and NO, and upregulates Nrf-2 and HO-1. Oleocanthal reduces Aβ deposition. Oleocanthal exhibits anti-Leishmania activity against promastigotes and amastigotes of L. major, with IC₅₀ values of 18.7 and 87 μg/mL, respectively. Oleocanthal exhibits anticancer activity against colon, breast, liver, and melanoma cancers. Oleocanthal also exhibits anti-inflammatory and neuroprotective properties. Oleocanthal can be used in Alzheimer's disease research.

Necrosulfonamide-d₄ is the deuterium labeled Necrosulfonamide (HY-100573). Necrosulfonamide is a MLKL and Gasdermin D (GSDMD) inhibitor, capable of separately inhibiting necroptosis and pyroptosis of cells. Necrosulfonamide does not affect the activation of upstream signals, but specifically inhibits the downstream executor oligomerization step. Necrosulfonamide reduces the expression of the key kinases NLRP3 and caspase-1 involved in necroptosis and pyroptosis, activate the Nrf2 pathway and the downstream antioxidant enzymes, and also downregulates a variety of inflammatory factors. Necrosulfonamide plays significant roles in various diseases such as neurodegenerative diseases (such as Parkinson’s disease), tissue damage and ischemia-reperfusion injury, inflammatory bowel disease, osteoarthritis and fracture repair, and hair loss by regulating two important programmed necrosis pathways.