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000289302 1001_ $$aNamoto, Kenji$$b0
000289302 245__ $$aNIBR-LTSi is a selective LATS kinase inhibitor activating YAP signaling and expanding tissue stem cells in vitro and in vivo.
000289302 260__ $$aAmsterdam [u.a.]$$bElsevier$$c2024
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000289302 520__ $$aThe YAP/Hippo pathway is an organ growth and size regulation rheostat safeguarding multiple tissue stem cell compartments. LATS kinases phosphorylate and thereby inactivate YAP, thus representing a potential direct drug target for promoting tissue regeneration. Here, we report the identification and characterization of the selective small-molecule LATS kinase inhibitor NIBR-LTSi. NIBR-LTSi activates YAP signaling, shows good oral bioavailability, and expands organoids derived from several mouse and human tissues. In tissue stem cells, NIBR-LTSi promotes proliferation, maintains stemness, and blocks differentiation in vitro and in vivo. NIBR-LTSi accelerates liver regeneration following extended hepatectomy in mice. However, increased proliferation and cell dedifferentiation in multiple organs prevent prolonged systemic LATS inhibition, thus limiting potential therapeutic benefit. Together, we report a selective LATS kinase inhibitor agonizing YAP signaling and promoting tissue regeneration in vitro and in vivo, enabling future research on the regenerative potential of the YAP/Hippo pathway.
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000289302 650_7 $$2Other$$aLATS kinase inhibitor
000289302 650_7 $$2Other$$aYAP agonist
000289302 650_7 $$2Other$$aYAP/Hippo pathway
000289302 650_7 $$2Other$$adrug development
000289302 650_7 $$2Other$$aliver regeneration
000289302 650_7 $$2Other$$aorganoid expansion
000289302 650_7 $$2Other$$aregenerative medicine
000289302 650_7 $$2Other$$atissue regeneration
000289302 650_7 $$2Other$$atissue stem cells
000289302 650_7 $$2Other$$awound healing
000289302 7001_ $$aBaader, Clara$$b1
000289302 7001_ $$aOrsini, Vanessa$$b2
000289302 7001_ $$aLandshammer, Alexandro$$b3
000289302 7001_ $$aBreuer, Eva$$b4
000289302 7001_ $$0P:(DE-He78)a887813af3adbee0648ab15f4f63972c$$aDinh, Kieu Trinh$$b5$$udkfz
000289302 7001_ $$aUngricht, Rosemarie$$b6
000289302 7001_ $$aPikiolek, Monika$$b7
000289302 7001_ $$aLaurent, Stephane$$b8
000289302 7001_ $$aLu, Bo$$b9
000289302 7001_ $$aAebi, Alexandra$$b10
000289302 7001_ $$aSchönberger, Katharina$$b11
000289302 7001_ $$aVangrevelinghe, Eric$$b12
000289302 7001_ $$aEvrova, Olivera$$b13
000289302 7001_ $$aSun, Tianliang$$b14
000289302 7001_ $$aAnnunziato, Stefano$$b15
000289302 7001_ $$aLachal, Julie$$b16
000289302 7001_ $$aRedmond, Emily$$b17
000289302 7001_ $$aWang, Louis$$b18
000289302 7001_ $$aWetzel, Kristie$$b19
000289302 7001_ $$aCapodieci, Paola$$b20
000289302 7001_ $$aTurner, Jonathan$$b21
000289302 7001_ $$aSchutzius, Gabi$$b22
000289302 7001_ $$aUnterreiner, Vincent$$b23
000289302 7001_ $$aTrunzer, Markus$$b24
000289302 7001_ $$aBuschmann, Nicole$$b25
000289302 7001_ $$aBehnke, Dirk$$b26
000289302 7001_ $$aMachauer, Rainer$$b27
000289302 7001_ $$aScheufler, Clemens$$b28
000289302 7001_ $$aParker, Christian N$$b29
000289302 7001_ $$aFerro, Magali$$b30
000289302 7001_ $$aGrevot, Armelle$$b31
000289302 7001_ $$aBeyerbach, Armin$$b32
000289302 7001_ $$aLu, Wei-Yu$$b33
000289302 7001_ $$aForbes, Stuart J$$b34
000289302 7001_ $$aWagner, Jürgen$$b35
000289302 7001_ $$aBouwmeester, Tewis$$b36
000289302 7001_ $$aLiu, Jun$$b37
000289302 7001_ $$aSohal, Bindi$$b38
000289302 7001_ $$aSahambi, Sukhdeep$$b39
000289302 7001_ $$aGreenbaum, Linda E$$b40
000289302 7001_ $$aLohmann, Felix$$b41
000289302 7001_ $$aHoppe, Philipp$$b42
000289302 7001_ $$aCong, Feng$$b43
000289302 7001_ $$aSailer, Andreas W$$b44
000289302 7001_ $$aRuffner, Heinz$$b45
000289302 7001_ $$aGlatthar, Ralf$$b46
000289302 7001_ $$aHumar, Bostjan$$b47
000289302 7001_ $$aClavien, Pierre-Alain$$b48
000289302 7001_ $$0P:(DE-He78)54a6641a6c26ddc49cc754740e90b438$$aDill, Michael T$$b49$$udkfz
000289302 7001_ $$aGeorge, Elizabeth$$b50
000289302 7001_ $$aMaibaum, Jürgen$$b51
000289302 7001_ $$aLiberali, Prisca$$b52
000289302 7001_ $$aTchorz, Jan S$$b53
000289302 773__ $$0PERI:(DE-600)2375356-0$$a10.1016/j.stem.2024.03.003$$gVol. 31, no. 4, p. 554 - 569.e17$$n4$$p554 - 569.e17$$tCell stem cell$$v31$$x1934-5909$$y2024
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