YS-49 monohydrate

YS 49 monohydrate inhibits Ang II-stimulated proliferation of VSMCs via induction of HO-1.IC50 value:Target: HO-1YS-49 is a novel positive inotropic isoquinoline compound. YS-49 has potential as a therapeutic strategy for the pathogenesis of Ang II-related vascular diseases such as hypertension and atherosclerosis, via the induction of HO-1 gene activity. YS-49 induced HO-1 protein production in a dose-and time-dependent manner in VSMCs. Treatment with YS-49 significantly and dose-dependently inhibited Ang II-induced VSMC proliferation, ROS production, and phosphorylation of JNK, but not P38 MAP kinase or ERK1/2.YS-49(32.8 microM) exhibited much stronger inhibitory effects on TXA(2) formation. The higher inhibitory potencies of YS-49 (IC(50): 3.3microM) than higenamine (IC(50): 140 microM) on AA induced rat platelet aggregation was presumed to be the result of low inhibitory effect of higenamine than YS-49 on TXA(2) production from AA. The oral administration of YS-49 (50 mg/kg) increased the recovery rates from the acute thrombotic challenge in mice and lowered the weight of thrombus formed inside the AV shunt tube in rats.

[1]. Kang YJ, et al. Prevention of the expression of inducible nitric oxide synthase by a novel positive inotropic agent, YS 49, in rat vascular smooth muscle and RAW 264.7 macrophages. Br J Pharmacol. 1999 Sep;128(2):357-64. [2]. Yun-Choi HS, et al. Antithrombotic effects of YS-49 and YS-51--1-naphthylmethyl analogs of higenamine. Thromb Res. 2001 Nov 15;104(4):249-55. [3]. Pyo MK, et al. Effects of two tetrahydroisoquinolines (YS-49 and YS-51) on experimental disseminated intravascular coagulation induced by lipopolysaccharide in rats. Arzneimittelforschung. 2004;54(11):705-10. [4]. Pyo MK, et al. Effects of higenamine and its 1-naphthyl analogs, YS-49 and YS-51, on platelet TXA2 synthesis and aggregation. Thromb Res. 2007;120(1):81-6.