{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T16:30:47Z","timestamp":1788453047156,"version":"build-2803163510"},"reference-count":37,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2023,3,8]],"date-time":"2023-03-08T00:00:00Z","timestamp":1678233600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Chronic heart failure, a progressive disease with limited treatment options currently available, especially in heart failure with preserved ejection fraction (HFpEF), represents an unmet medical need as well as an economic burden. The development of a novel therapeutic to slow or reverse disease progression would be highly impactful to patients and society. Relaxin\u20102 (relaxin) is a human hormone regulating cardiovascular, renal, and pulmonary adaptations during pregnancy. A short\u2010acting recombinant relaxin, Serelaxin, demonstrated short\u2010term heart failure symptom relief and biomarker improvement in acute heart failure trials. Here, we present the development of a long\u2010acting relaxin analogue to be tested in the treatment of chronic heart failure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>LY3540378 is a long\u2010acting protein therapeutic composed of a human relaxin analogue and a serum albumin\u2010binding VHH domain.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>LY3540378 is a potent agonist of the relaxin family peptide receptor 1 (RXFP1) and maintains selectivity against RXFP2\/3\/4 comparable to native relaxin. The half\u2010life of LY3540378 in preclinical species is extended through high affinity binding of the albumin\u2010binding VHH domain to serum albumin. When tested in a single dose administration, LY3540378 elicited relaxin\u2010mediated pharmacodynamic responses, such as reduced serum osmolality and increased renal blood flow in rats. In an isoproterenol\u2010induced cardiac hypertrophy mouse model, treatment with LY3540378 significantly reduced cardiac hypertrophy and improved isovolumetric relaxation time. In a monkey cardiovascular safety study, there were no adverse observations from administration of LY3540378.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>LY3540378 demonstrated to be a suitable clinical development candidate, and is progressing in clinical trials.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.16055","type":"journal-article","created":{"date-parts":[[2023,2,13]],"date-time":"2023-02-13T23:39:05Z","timestamp":1676331545000},"page":"1965-1980","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Development of a long\u2010acting relaxin analogue, LY3540378, for treatment of chronic heart failure"],"prefix":"10.1111","volume":"180","author":[{"given":"Petra","family":"Verdino","sequence":"first","affiliation":[{"name":"Lilly Research Laboratories Eli Lilly and Company  Indianapolis Indiana 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