%0 Journal Article
%A Zwirner, Stefan
%A Abu Rmilah, Anan A
%A Klotz, Sabrina
%A Pfaffenroth, Bent
%A Kloevekorn, Philip
%A Moschopoulou, Athina A
%A Schuette, Svenja
%A Haag, Mathias
%A Selig, Roland
%A Li, Kewei
%A Zhou, Wei
%A Nelson, Erek
%A Poso, Antti
%A Chen, Harvey
%A Amiot, Bruce
%A Jia, Yao
%A Minshew, Anna
%A Michalak, Gregory
%A Cui, Wei
%A Rist, Elke
%A Longerich, Thomas
%A Jung, Birgit
%A Felgendreff, Philipp
%A Trompak, Omelyan
%A Premsrirut, Prem K
%A Gries, Katharina
%A Muerdter, Thomas E
%A Heinkele, Georg
%A Wuestefeld, Torsten
%A Shapiro, David
%A Weissbach, Markus
%A Koenigsrainer, Alfred
%A Sipos, Bence
%A Ab, Eiso
%A Zacarias, Magdalena Ortiz
%A Theisgen, Stephan
%A Gruenheit, Nicole
%A Biskup, Saskia
%A Schwab, Matthias
%A Albrecht, Wolfgang
%A Laufer, Stefan
%A Nyberg, Scott
%A Zender, Lars
%T First-in-class MKK4 inhibitors enhance liver regeneration and prevent liver failure.
%J Cell
%V 187
%N 7
%@ 0092-8674
%C New York, NY
%I Elsevier
%M DKFZ-2024-00544
%P 1666-1684.e26
%D 2024
%Z 2024 Mar 28;187(7):1666-1684.e26
%X Diminished hepatocyte regeneration is a key feature of acute and chronic liver diseases and after extended liver resections, resulting in the inability to maintain or restore a sufficient functional liver mass. Therapies to restore hepatocyte regeneration are lacking, making liver transplantation the only curative option for end-stage liver disease. Here, we report on the structure-based development and characterization (nuclear magnetic resonance [NMR] spectroscopy) of first-in-class small molecule inhibitors of the dual-specificity kinase MKK4 (MKK4i). MKK4i increased liver regeneration upon hepatectomy in murine and porcine models, allowed for survival of pigs in a lethal 85
%K MKK4 (Other)
%K drug discovery and development (Other)
%K first-in-human phase I trial (Other)
%K liver (Other)
%K liver failure (Other)
%K liver regeneration (Other)
%K partial hepatectomy (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:38490194
%R 10.1016/j.cell.2024.02.023
%U https://inrepo02.dkfz.de/record/289012