This technology provides pharmaceutical and food compositions for preventing and treating valvular calcification diseases, such as valvulopathy and aortic stenosis, using quinoline-3-carboxamide compounds—represented by paquinimod, tasquinimod, and laquinimod—or their salts as active ingredients. These compounds inhibit the expression of calcification and related protein markers in valvular interstitial cells.
Aortic stenosis is a major cardiovascular disease where inflammation and calcification restrict valve opening. Without treatment, the mortality rate reaches 50% within two years of symptom onset, yet no effective medication currently exists. The only standard treatment, valve replacement surgery, is burdensome for elderly patients, costing approximately 30 million KRW and carrying risks of stroke, paravalvular leakage, and artificial valve durability issues. Clinical trials repurposing hyperlipidemia or osteoporosis drugs, such as PCSK9 inhibitors or niacin, have shown limited efficacy as they are not specific to valvular calcification.
This technology is based on the discovery that compounds of Formula 1—where R1 is ethyl, methoxy, or chlorine; R2 is hydrogen or trifluoromethyl; and R3 is methyl or ethyl—prevent the osteogenic transition of valvular interstitial cells, thereby inhibiting the calcification markers OPN and RUNX2. The composition is designed for a daily dosage of 0.001 to 10 g. It can be applied as a treatment to slow the progression of aortic stenosis in the elderly, as an adjuvant therapy for valve replacement surgery, or as a functional food for cardiovascular health, offering an oral alternative to surgery and reducing the burden on high-risk elderly patients.
This invention was developed with support from the Ministry of Science and ICT for the discovery of biomarkers and therapeutic targets to inhibit intractable aortic valve calcification using multi-omics data-based deep learning.
EP4483878A1, US2025-0235444A1, WO2023-204511A1
