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Volenrelaxin (LY3540378) is a long-acting recombinant human relaxin protein developed by Eli Lilly and Company for the treatment of chronic heart failure with preserved ejection fraction (HFpEF). It is engineered as a fusion protein consisting of an immunoglobulin G (IgG) domain against serum albumin, fused to human relaxin-2 chains. This design extends its half-life in circulation via high-affinity binding to serum albumin. Volenrelaxin acts as a potent agonist of the relaxin family peptide receptor 1 (RXFP1), mimicking the effects of endogenous relaxin hormone, which regulates cardiovascular, renal, and pulmonary adaptations. Preclinical studies demonstrated that volenrelaxin increases renal plasma flow, reduces cardiac hypertrophy, improves diastolic function, lowers blood pressure, and enhances kidney perfusion without significant adverse effects. The drug was administered subcutaneously in clinical trials but development for HFpEF was terminated after interim analysis due to lack of efficacy on heart failure events[2][4][5][6].
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