HO-1 Agonist

(-)-(E)-Guggulsterone ((E)-Guggulsterone) is an orally active natural stereoisomer of Guggulsterone (HY-107738). (-)-(E)-Guggulsterone is an antagonist for the Farnesoid X Receptor (FXR) with an IC₅₀ of 24.06 μM and possesses potent hypolipidemic properties. (-)-(E)-Guggulsterone suppresses dengue virus (DENV) replication by upregulating antiviral interferon responses by inducing HO-1 expression via Nrf2 activation. (-)-(E)-Guggulsterone exhibits antibacterial activities against Bacillus subtilis, Staphylococcus aureus and Pseudomonas aeruginosa. (-)-(E)-Guggulsterone has cardiac protective and antioxidant activities in rats.

Pellitorine is a bioactive natural amide compound. Pellitorine can competitively antagonize the activation of TRPV1 by Capsaicin (HY-10448), thereby reducing pain signal transmission. Pellitorine improves cognitive dysfunction by upregulating the BDNF-ERK1/2-CREB and Nrf2-HO-1 pathways. Pellitorine exerts anti-inflammatory and anti-sepsis effects by inhibiting the release of high mobility group protein B1 (HMGB1) and the expression of RAGE/TLR4. Pellitorine exerts its antithrombotic effect by prolonging the clotting time, inhibiting the activity of clotting factors and thrombin. Pellitorine inhibits lipid peroxidation and resists ferroptosis by upregulating GPX4 and DHODH. Pellitorine kills Aedes aegypti mosquito larvae by inhibiting V-type H⁺-ATPase and aquaporin 4 (AaAQP4). Pellitorine exhibits anti-cancer activity (e.g., leukemia and breast cancer) and has inhibitory effects on certain bacteria.

NF-κB-IN-20 is an orally active NF-κB inhibitor. NF-κB-IN-20 directly binds to the Keap1 protein, activating the Keap1/Nrf2/HO-1 antioxidant pathway, and simultaneously inhibiting the NF-κB inflammatory pathway, thereby synergistically reducing oxidative stress and inflammatory responses. NF-κB-IN-20 M11 inhibits the expression of IL-6, IL-1β, and TNF-α, significantly reduces the level of ROS, and restores the mitochondrial membrane potential. NF-κB-IN-20 can be used for the study of acute lung injury (ALI).