1.MOA

The dugs for heart failure on the market primarily work by regulating the neuroendocrine system and reducing peripheral resistance to lessen the heart‘s workload. However, there is no drug that directly improves cardiac remodeling and heart function to treat heart failure

Single-cell sequencing analysis revealed that fibroblasts, mediating myocardial fibrosis, could be divided into three clusters, including cluster I, II, III(Showed in Figure 1, A). The number of fibroblast cluster I was significantly increased in the heart of HCM and DCM patients (HF)(Showed in Figure 1, B). GO enrichment analysis showed that significant activation of target-related pathways in fibroblast I(Showed in Figure 1,C). Target X-related pathways are activated in the heart of HCM and DCM patients (HF).

Target X is on the upstream of MRTF-A, and it can regulate the nuclear translocation of transcriptional cofactor MRTF-A and colocalization with transcriptional factor SRF. MRTF-A takes part in cardiac remodeling and fibrosis in response to the renin-angiotensin system and post-MI remodeling.

Asset disrupts the nuclear translocation of MRTF-A and the colocalization with SRF by inhibiting Target X, which decreases the expression of Collagen and Fibronectin in cardiomyocytes to improve cardiac remodeling and fibrosis；

2.Highlights

Improve cardiac function and protects against myocardial injury and fibrosis in mice on day 7 after LAD ligation
Asset obviously reduced the deposition of collagen and myocardial fibrosis；
Asset obviously reduced myocardial hypertrophy；

Improves cardiac function and myocardial recovery in LAD-induced heart failure in rats after 21 days
Asset obviously reduced collagen deposition and fibrosis;
Asset obviously reduced myocardial hypertrophy;

Excellent renal protective activity

Long-term treatment (8 weeks) with asset significantly ameliorated renal injury andrenal fibrosis in hypertensive rats；
Asset significantly protectedagainst renal fibrosis in salt-sensitive rats；
Asset amelioratedrenal fibrosis and reduced basement membrane thickening in diabetic nephropathy mice；

Better Safety