{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T08:27:47Z","timestamp":1793262467821,"version":"4.5.0"},"reference-count":67,"publisher":"American Society for Clinical Investigation","issue":"9","license":[{"start":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T00:00:00Z","timestamp":1746662400000},"content-version":"vor","delay-in-days":35,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"TYRA Biosciences, Inc.","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"https:\/\/ror.org\/008a2q193","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,5,8]]},"abstract":"<jats:p>\n                    Achondroplasia (ACH) and hypochondroplasia (HCH), the two most common types of dwarfism, are each caused by\n                    <jats:italic>FGFR3<\/jats:italic>\n                    gain-of-function mutations that result in increased FGFR3 signaling, which disrupts chondrogenesis and osteogenesis, resulting in disproportionately shortened long bones. In this study, TYRA-300, a potent and selective FGFR3 inhibitor, was evaluated in 3 genetic contexts: wild-type mice, the\n                    <jats:italic>\n                      Fgfr3\n                      <jats:sup>Y367C\/+<\/jats:sup>\n                    <\/jats:italic>\n                    mouse model of ACH, and the\n                    <jats:italic>\n                      Fgfr3\n                      <jats:sup>N534K\/+<\/jats:sup>\n                    <\/jats:italic>\n                    mouse model of HCH. In each model, TYRA-300 treatment increased nasoanal length and tibia and femur length. In the two FGFR3-altered models, TYRA-300\u2013induced growth partially restored the disproportionality of long bones. Histologic analysis of the growth plate in\n                    <jats:italic>\n                      Fgfr3\n                      <jats:sup>Y367C\/+<\/jats:sup>\n                    <\/jats:italic>\n                    mice revealed that TYRA-300 mechanistically increased both proliferation and differentiation of chondrocytes. Importantly, children with ACH can experience medical complications due to foramen magnum stenosis, and TYRA-300 significantly improved the size and shape of the skull and foramen magnum in\n                    <jats:italic>\n                      Fgfr3\n                      <jats:sup>Y367C\/+<\/jats:sup>\n                    <\/jats:italic>\n                    mice. Spinal stenosis is also a frequent complication, and TYRA-300 increased the lumbar vertebrae length and improved the shape of the intervertebral discs in both models. Taken together, these studies demonstrate that the selective FGFR3 inhibitor TYRA-300 led to a significant increase in bone growth in two independent FGFR3-driven preclinical models as well as in wild-type mice.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.189307","type":"journal-article","created":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T12:35:54Z","timestamp":1743683754000},"source":"Crossref","is-referenced-by-count":7,"title":["TYRA-300, an FGFR3-selective inhibitor, promotes bone growth in two FGFR3-driven models of chondrodysplasia"],"prefix":"10.1172","volume":"10","author":[{"given":"Jacqueline H.","family":"Starrett","sequence":"first","affiliation":[{"name":"Tyra Biosciences, Carlsbad, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Lemoine","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Paris Cit\u00e9, Imagine Institute, Laboratory of Molecular and Physiopathological Bases of 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