{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T09:15:18Z","timestamp":1783674918840,"version":"3.55.0"},"reference-count":54,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>Relaxin is a naturally occurring peptide hormone with significant cardiovascular effects, particularly during the adaptation to pregnancy. A short\u2010acting peptide therapeutic previously demonstrated pharmacological effects in acute heart failure. TX000045 (\u2018TX45\u2019) is a long\u2010acting relaxin being developed for the treatment of pulmonary hypertension.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>TX45 is human relaxin\u20102 fused to the C\u2010terminus of the Fc domain of human IgG1, wherein the B and A chains of human relaxin are connected by a peptide linker. Protein engineering optimized the biophysical properties through adjustment of the isoelectric point. Preclinical animal models confirmed extended half\u2010life and known pharmacodynamic (PD) vasodilator effects on renal plasma flow. TX45 decreased inflammation, cardiac hypertrophy and pulmonary arterial muscularization in a monocrotaline (MCT) rat pulmonary hypertension model. First\u2010in\u2010human studies evaluated pharmacokinetic (PK) and PD in a double\u2010blind, placebo\u2010controlled, single ascending dose study in healthy subjects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>TX45 significantly improved biophysical and PK\/PD properties, relative to unmodified versions. TX45 clearly decreased pulmonary hypertension in the MCT rat model. In healthy human subjects, TX45 was well\u2010tolerated with a terminal elimination half\u2010life of 2\u20133\u00a0weeks and increased renal plasma flow. Repeated measures of renal plasma flow after single doses of TX45 were used to create an exposure\u2013response model that enabled Phase 2 dose selection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>TX45 is an extended half\u2010life relaxin with PK and PD properties consistent with a relaxin mimetic. TX45 was well tolerated in early clinical studies. Preclinical PK\/PD data predicted human PK\/PD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70498","type":"journal-article","created":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T02:35:58Z","timestamp":1779503758000},"page":"5062-5081","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Development of a long\u2010acting relaxin for the treatment of pulmonary hypertension"],"prefix":"10.1111","volume":"183","author":[{"given":"John","family":"Diener","sequence":"first","affiliation":[{"name":"Tectonic Therapeutic, Inc.  Watertown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitesh","family":"Soni","sequence":"additional","affiliation":[{"name":"Tectonic Therapeutic, Inc.  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Garcia A. Paterson J. C. Gao C. &Sermadiras I.(2018).Relaxin fusion polypeptides and uses thereof (World Intellectual Property Organization Patent No. WO2018138170A1).https:\/\/patents.google.com\/patent\/WO2018138170A1\/en"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines13020299"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1065654"},{"key":"e_1_2_12_20_1","unstructured":"Kim S. S. Yang P. Yung L.\u2010M. Myhr C. B. Augur Z. M. VanDeusen C. Bocobo G. A. Dinter T. Cavallo J. Chain D. Dwyer S. C. Southwood M. Jia Z. Morrell N. W. Illiano S. Ferrer M. Wilson K. J. Southall N. Sanderson P. Agoulnik I.U. Marugan J.J. AlexanderIAgoulnik A.I. Yu P. B.(2019).Biased Relaxin\u2010RXFP1 Agonist ML290 Attenuates the Development of Pulmonary Hypertension. 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