A novel lipoprotein (a) lowering drug, D-47, decreases neointima thickening after vascular injury

Abstract

: Although Lp(a) have been thought to be a cardiovascular risk factor, it is unclear whether lowering Lp(a) levels reduces the risk of cardiovascular diseases. No pharmacological agents which selectively reduce serum Lp(a) levels, and Lp(a) is present in primate but absent in common laboratory animals such as mice and pigs. In the present study we used transgenic mice of human Lp(a) and tested effect a novel Lp(a) lowering drug D-47 on neointima formation after vascular injury. D-47 successfully decreased plasma levels of Lp(a) and possibly inhibited neointima formation in Lp(a) transgenic mice. The results indicate that we can modulate plasma Lp(a) levels by pharmacologic agents and inhibit atherogenic properties of Lp(a) by reducing plasma levels of Lp(a).

Ameliorating effects of D-47, a newly developed compound, on lipid metabolism in an animal model of familial hypercholesterolemia (WHHLMI rabbits)

“…Although a potent lipid lowering compound, S-2E, was previously developed (Ohmori et al, 2003;Ohmori et al, 2004), the absorption in intestine was very low. In order to improve the intestine absorption of S-2E, S-2E-arginine salt (a derivative of S-2E), was developed (Ogawa et al, 2016;Nakaya et al, 2017), and a solid dispersion of S-2E-arginine salt (D-47) was developed. In the present study, we examined the effects of D-47 on serum lipid levels, lipid contents in the liver, fat accumulation in tissues, and body weight using WHHLMI rabbits.…”

“…Materials and methods 7 2.1. Materials D-47 was produced in Tokushima-Bunri University (Tokushima, Japan), and is a solid dispersion of the S-2E-arginine salt (C28H38N5O6, MW: 540, PubChem CID: 9864020) (Nakaya et al, 2017). The solubility and plasma concentration of the S-2E-arginine salt were markedly improved by making it a solid dispersion (Supplemental Table 1).…”