LOX-1 Inhibitor

Gocdacimab (MEDI6570) is a fully human IgG1 monoclonal antibody inhibitor targeting the lectin-like oxidized low-density lipoprotein receptor LOX-1. By binding to LOX-1 and blocking its function, gocdacimab effectively reduces the level of free soluble LOX-1, thereby inhibiting key pathological processes such as lipid accumulation, foam cell formation, and vascular wall inflammation. Gocdacimab can interfere with atherosclerosis-related mechanisms, and it is used for research on atherosclerosis, and type 2 diabetes mellitus.

Lactupicrin (Lactucopicrin) exhibits analgesic, sedative, antimalarial activities and atheroprotective effect. Lactupicrin inhibits acetylcholinesterase (AChE) with an IC₅₀ of 150.3 μM. Lactupicrin is an orally active characteristic bitter sesquiterpene lactone.

Kansuinine A is a diterpenoid compound. Kansuinine A is isolated from the roots of Euphorbia kansui. Kansuinine A inhibits H₂O₂-mediated upregulation of phosphorylated IKKβ, NF-κB and IκBα. Kansuinine A inhibits ROS production, reduces the Bax/Bcl-2 ratio and the expression of cleaved Caspase-3. Kansuinine A upregulates the expression of SOCS-3 and blocks IL-6-induced signal transduction. Kansuinine A decreases the expression of LOX-1 and inhibits Apoptosis. Kansuinine A reduces the atherosclerotic lesion area of the aortic arch, improves glucose/insulin tolerance, and enhances antioxidant capacity. Kansuinine A exhibits antiviral and antitumor activities. Kansuinine A can be used in research related to atherosclerosis, liver cancer and type 2 diabetes.

DKI5, also known as (E)-N’-benzylidenehydrazinecarbothiohydrazide, is a LOX-1 inhibitor with an IC₅₀ value of 22.5 μM.

COX-2-IN-30 is a benzenesulfonamide derivative, as well as an orally active and dual inhibitor of COX (IC₅₀=49 nM for COX-2, 10.4 μM for COX-1) and 5-LOX (IC₅₀=2.4 μM). COX-2-IN-30 also inhibits transmembrane hCA IX and hCA XII isoform with nanomolar calss K_i values. COX-2-IN-30 exhibits analgesic, anti-inflammatory, and ulcerogenic activities, and does not show acute gastric effect.

COX-2/5-LOX-IN-4 (Compound 1) is a dual inhibitor that acts on both COX-2 and 5-LOX, with IC₅₀ values of 0.05 μM for COX-2 and 0.003 μM for 5-LOX. By inhibiting the arachidonic acid metabolism pathway, COX-2/5-LOX-IN-4 reduces the production of prostaglandins and leukotrienes, alleviating inflammatory responses. In a rat ear edema model, intravenous administration (0.01 and 0.1 mg/kg) reduced edema by 41% and 44%, respectively, demonstrating significant anti-inflammatory effects. COX-2/5-LOX-IN-4 shows promise for studying the mechanisms of inflammatory diseases.

15-LOX-1 inhibitor 2 (Compound 5i) is an inhibitor of 15-lipoxygenase-1 (15-LOX-1) with an IC₅₀ of 1.7 μM. 15-LOX-1 inhibitor 2 inhibits the activity of 15-LOX-1 enzyme, reduces the production of lipid peroxides, thereby inhibiting lipid peroxidation and protecting cells from cell death induced by RSL3 (HY-100218A). 15-LOX-1 inhibitor 2 can be used in research on cell death mechanisms, oxidative stress-related diseases and other fields.

AChE-IN-82 (compound 49) is an acetylcholinesterase (AChE) inhibitor. AChE-IN-82 inhibits eeAChE, eqBChE, hMAO-A, hMAO-B, and BACE-1 with IC₅₀s of 0.072, 9.81, 14.52, 0.024, 2.42 μM, respectively. AChE-IN-82 inhibits COX-1, COX-2 and 5-LOX with IC₅₀s of 60.41, 0.187, 0.18 μM, respectively. AChE-IN-82 shows an excellent neuroprotective effect by significantly reducing oxidative stress induced by H₂ O₂.