CHF5074 (CSP-1103) stabilizes human transthyretin in mice humanized at the transthyretin and retinol-binding protein loci

FEBS Letters
Yanshuang MuZhenghua Li

Abstract

Familial amyloidotic polyneuropathy is one type of protein misfolding disease. Transthyretin (TTR) tetramer dissociation is the limiting step for amyloid fibril formation. CHF5074 (CSP-1103) stabilizes TTR tetramer in vitro by binding to the T4 binding site. Here, we used three strains of double humanized mice (mTtr(hTTRVal30/hTTRVal30), mTtr(hTTRVal30/hTTRMet30), and mTtr(hTTRMet30/hTTRMet30)) to assess whether CHF5074 stabilizes TTR tetramers in vivo. Treatment of mice with CHF5074 increased serum TTR levels by stabilizing TTR tetramers. Although the binding affinities of CHF5074 and diflunisal with TTRMet30 were similar, CHF5074 bound TTRVal30 more strongly than did diflunisal, suggesting the potent TTR-stabilizing activity of CHF5074.

References

Dec 24, 1996·Proceedings of the National Academy of Sciences of the United States of America·G J MiroyJ W Kelly
Oct 28, 1998·Proceedings of the National Academy of Sciences of the United States of America·S A PetersonJ W Kelly
Feb 17, 1999·Bioorganic & Medicinal Chemistry Letters·V B OzaJ W Kelly
Mar 31, 2000·Nature Structural Biology·T KlabundeJ C Sacchettini
Aug 31, 2001·JAMA : the Journal of the American Medical Association·D MukherjeeE J Topol
Sep 28, 2002·Proceedings of the National Academy of Sciences of the United States of America·Per HammarströmJeffery W Kelly
Jan 30, 2003·Clinical Chemistry and Laboratory Medicine : CCLM·Gerhard Schreiber
Oct 30, 2003·Journal of the American Chemical Society·Nora S GreenJeffery W Kelly
Jan 9, 2004·Journal of Medicinal Chemistry·Sara L Adamski-WernerJeffery W Kelly
Feb 18, 2004·Laboratory Investigation; a Journal of Technical Methods and Pathology·Sean R MillerJeffery W Kelly
Feb 3, 2005·Bioorganic & Medicinal Chemistry Letters·Hossein RazaviJeffery W Kelly
Nov 17, 2006·Amyloid : the International Journal of Experimental and Clinical Investigation : the Official Journal of the International Society of Amyloidosis·Yoshiki SekijimaJeffery W Kelly
Feb 13, 2007·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Bruno P ImbimboAlberta Leon
Nov 27, 2008·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Gang ZhaoKen-ichi Yamamura
Dec 17, 2008·Current Pharmaceutical Design·Yoshiki SekijimaShu-ichi Ikeda
Feb 16, 2011·Journal of Alzheimer's Disease : JAD·Claudia BalducciRobert Nisticò
May 5, 2011·Frontiers in Neuroscience·Y-F TanJ M Wojtowicz
May 31, 2012·Proceedings of the National Academy of Sciences of the United States of America·Christine E BulawaRichard Labaudinière
May 30, 2013·Proceedings of the National Academy of Sciences of the United States of America·Sravan C PenchalaMamoun M Alhamadsheh

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Citations

Apr 20, 2016·PloS One·Irina IakovlevaAnders Olofsson
Apr 11, 2017·Amyloid : the International Journal of Experimental and Clinical Investigation : the Official Journal of the International Society of Amyloidosis·Lixia QiangZhenghua Li
Jan 14, 2018·Laboratory Investigation; a Journal of Technical Methods and Pathology·Xiangshun LiZhenghua Li
Jul 4, 2019·Expert Review of Clinical Pharmacology·Morie A GertzLaura Obici
Aug 2, 2019·Brain and Behavior·Morie A GertzTeresa Coelho
Feb 26, 2021·The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques·Monica AlcantaraVera Bril
Aug 17, 2021·Cardiology in Review·Matthew Capustin, William H Frishman

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