{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T19:30:21Z","timestamp":1790191821411,"version":"4.1.0"},"reference-count":65,"publisher":"Wiley","issue":"22","license":[{"start":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T00:00:00Z","timestamp":1753142400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T00:00:00Z","timestamp":1753142400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100010260","name":"Xiamen Southern Oceanographic Center","doi-asserted-by":"publisher","award":["23YYZP020QCB26"],"award-info":[{"award-number":["23YYZP020QCB26"]}],"id":[{"id":"10.13039\/501100010260","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>Large tumor suppressor kinases (LATS1 and 2) are core kinases of the Hippo signalling pathway, directly phosphorylate and inactivate the transcriptional coactivator Yes\u2010associated protein 1 (YAP), playing a pivotal role in cell self\u2010renewal and tissue regeneration. Hippo signalling inhibitors are urgently needed, both as tools for pharmacological studies of the Hippo pathway and as leads for developing novel, molecularly targeted drugs for the treatment of tissue injury and regeneration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      An enzyme linked immunosorbent assay (ELISA)\u2010based\n                      <jats:italic>in vitro<\/jats:italic>\n                      high\u2010throughput biochemical assay was used to the identification of a potent and reversible LATS1\/2 inhibitor, N\u2010(2\u2010chloro\u20106\u2010fluorobenzyl)\u20105\u2010(1H\u2010pyrrolo[2,3\u2010b] pyridin\u20103\u2010yl) furan\u20103\u2010carboxamide (named as LPi\u20101). The regulation of LPi\u20101 on the activity of LATS1\/2 kinases and YAP was evaluated both\n                      <jats:italic>in vitro<\/jats:italic>\n                      and\n                      <jats:italic>in vivo<\/jats:italic>\n                      . The murine models, including partial hepatectomy, paracetamol (acetaminophen\/APAP)\u2010induced liver hepatotoxicity and chemically induced colitis, were established to investigate the effect of LPi\u20101 on tissue repair and regeneration after injuries.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      LPi\u20101 effectively inhibited the activity of LATS1\/2 kinases, thereby facilitating YAP activation to enhance the proliferation of hepatocytes\n                      <jats:italic>in vi<\/jats:italic>\n                      tro. Moreover, LPi\u20101 was able to augment intestinal repair in mice following dextran sulphate sodium salt (DSS) treatment, as well as liver repair and regeneration in mice subjected to two\u2010thirds partial hepatectomy or APAP\u2010induced liver injury.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>In conclusion, LPi\u20101 can serve as a valuable tool compound for exploring diverse biological functions associated with LATS1\/2 kinases, as well as a promising lead compound for developing targeted therapeutic strategies aimed at enhancing tissue repair and regeneration.<\/jats:p>\n                  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