CSP-1103 (CHF5074) stabilizes human transthyretin in healthy human subjects

References

• Schreiber G. The evolution of transthyretin synthesis in the choroid plexus. Clin Chem Lab Med. 2002;40:1200–1210.
   PubMed Web of Science ®Google Scholar
• Vranckx R, Savu L, Maya M, et al. Characterization of a major development-regulated serum thyroxine-binding globulin in the euthyroid mouse. Biochem J. 1990;271:373–379.
   PubMed Web of Science ®Google Scholar
• Colon W, Kelly JW. Partial denaturation of transthyretin is sufficient for amyloid fibril formation in vitro. Biochemistry. 1992;31:8654–8660.
   PubMed Web of Science ®Google Scholar
• Hammarstrom P, Jiang X, Hurshman AR, et al. Sequence-dependent denaturation energetics: a major determinant in amyloid disease diversity. Proc Natl Acad Sci USA. 2002;99 Suppl 4:16427–16432.
   PubMed Web of Science ®Google Scholar
• Lai Z, Colon W, Kelly JW. The acid-mediated denaturation pathway of transthyretin yields a conformational intermediate that can self-assemble into amyloid. Biochemistry. 1996;35:6470–6482.
   PubMed Web of Science ®Google Scholar
• Johnson SM, Wiseman RL, Sekijima Y, et al. Native state kinetic stabilization as a strategy to ameliorate protein misfolding diseases: a focus on the transthyretin amyloidoses. Acc Chem Res. 2005;38:911–921.
   PubMed Web of Science ®Google Scholar
• Klabunde T, Petrassi HM, Oza VB, et al. Rational design of potent human transthyretin amyloid disease inhibitors. Nat Struct Biol. 2000;7:312–321.
   PubMedGoogle Scholar
• Miroy GJ, Lai Z, Lashuel HA, et al. Inhibiting transthyretin amyloid fibril formation via protein stabilization. Proc Natl Acad Sci USA. 1996;93:15051–15056.
   PubMed Web of Science ®Google Scholar
• Sekijima Y, Kelly JW, Ikeda S. Pathogenesis of and therapeutic strategies to ameliorate the transthyretin amyloidoses. Curr Pharm Des. 2008;14:3219–3230.
   PubMed Web of Science ®Google Scholar
• Porrini V, Lanzillotta A, Branca C, et al. CHF5074 (CSP-1103) induces microglia alternative activation in plaque-free Tg2576 mice and primary glial cultures exposed to beta-amyloid. Neuroscience. 2015;302:112–120.
   PubMed Web of Science ®Google Scholar
• Balducci C, Mehdawy B, Mare L, et al. The gamma-secretase modulator CHF5074 restores memory and hippocampal synaptic plasticity in plaque-free Tg2576 mice. J Alzheimers Dis. 2011;24:799–816.
   PubMed Web of Science ®Google Scholar
• Imbimbo BP, Del Giudice E, Cenacchi V, et al. In vitro and in vivo profiling of CHF5022 and CHF5074 two beta-amyloid1-42 lowering agents. Pharmacol Res. 2007;55:318–328.
   PubMed Web of Science ®Google Scholar
• Imbimbo BP, Del Giudice E, Colavito D, et al. 1-(3',4'-Dichloro-2-fluoro[1,1'-biphenyl]-4-yl)-cyclopropanecarboxylic acid (CHF5074), a novel gamma-secretase modulator, reduces brain beta-amyloid pathology in a transgenic mouse model of Alzheimer's disease without causing peripheral toxicity. J Pharmacol Exp Ther. 2007;323:822–830.
   PubMed Web of Science ®Google Scholar
• Imbimbo BP, Giardino L, Sivilia S, et al. CHF5074, a novel gamma-secretase modulator, restores hippocampal neurogenesis potential and reverses contextual memory deficit in a transgenic mouse model of Alzheimer's disease. J Alzheimers Dis. 2010;20:159–173.
   PubMed Web of Science ®Google Scholar
• Imbimbo BP, Hutter-Paier B, Villetti G, et al. CHF5074, a novel gamma-secretase modulator, attenuates brain beta-amyloid pathology and learning deficit in a mouse model of Alzheimer's disease. Br J Pharmacol. 2009;156:982–993.
   PubMed Web of Science ®Google Scholar
• Zanotti G, Cendron L, Folli C, et al. Structural evidence for native state stabilization of a conformationally labile amyloidogenic transthyretin variant by fibrillogenesis inhibitors. FEBS Lett. 2013;587:2325–2331.
   PubMed Web of Science ®Google Scholar
• Zhao G, Li Z, Araki K, et al. Inconsistency between hepatic expression and serum concentration of transthyretin in mice humanized at the transthyretin locus. Genes Cells. 2008;13:1257–1268.
   PubMed Web of Science ®Google Scholar
• Mu Y, Jin S, Shen J, et al. CHF5074 (CSP-1103) stabilizes human transthyretin in mice humanized at the transthyretin and retinol-binding protein loci. FEBS Lett. 2015;589:849–856.
   PubMed Web of Science ®Google Scholar
• Imbimbo BP, Frigerio E, Breda M, et al. Pharmacokinetics and pharmacodynamics of CHF5074 after short-term administration in healthy subjects. Alzheimer Dis Assoc Disord. 2013;27:278–286.
   PubMed Web of Science ®Google Scholar
• Sekijima Y, Wiseman RL, Matteson J, et al. The biological and chemical basis for tissue-selective amyloid disease. Cell. 2005;121:73–85.
   PubMed Web of Science ®Google Scholar
• Bulawa CE, Connelly S, Devit M, et al. Tafamidis, a potent and selective transthyretin kinetic stabilizer that inhibits the amyloid cascade. Proc Natl Acad Sci USA. 2012;109:9629–9634.
   PubMed Web of Science ®Google Scholar
• Pullakhandam R, Srinivas PN, Nair MK, et al. Binding and stabilization of transthyretin by curcumin. Arch Biochem Biophys. 2009;485:115–119.
   PubMed Web of Science ®Google Scholar
• Raghu P, Reddy GB, Sivakumar B. Inhibition of transthyretin amyloid fibril formation by 2,4-dinitrophenol through tetramer stabilization. Arch Biochem Biophys. 2002;400:43–47.
   PubMed Web of Science ®Google Scholar
• Sekijima Y, Dendle MA, Kelly JW. Orally administered diflunisal stabilizes transthyretin against dissociation required for amyloidogenesis. Amyloid. 2006;13:236–249.
   PubMed Web of Science ®Google Scholar
• Tojo K, Sekijima Y, Kelly JW, et al. Diflunisal stabilizes familial amyloid polyneuropathy-associated transthyretin variant tetramers in serum against dissociation required for amyloidogenesis. Neurosci Res. 2006;56:441–449.
   PubMed Web of Science ®Google Scholar
• Gupta S, Chhibber M, Sinha S, et al. Design of mechanism-based inhibitors of transthyretin amyloidosis: studies with biphenyl ethers and new structural templates. J Med Chem. 2007;50:5589–5599.
   PubMed Web of Science ®Google Scholar
• Hammarstrom P, Jiang X, Deechongkit S, et al. Anion shielding of electrostatic repulsions in transthyretin modulates stability and amyloidosis: insight into the chaotrope unfolding dichotomy. Biochemistry. 2001;40:11453–11459.
   PubMed Web of Science ®Google Scholar
• Steelman SL, Cirillo VJ, Tempero KF. The chemistry, pharmacology and clinical pharmacology of diflunisal. Curr Med Res Opin. 1978;5:506–514.
   PubMed Web of Science ®Google Scholar
• Miller SR, Sekijima Y, Kelly JW. Native state stabilization by NSAIDs inhibits transthyretin amyloidogenesis from the most common familial disease variants. Lab Invest. 2004;84:545–552.
   PubMed Web of Science ®Google Scholar
• Adamski-Werner SL, Palaninathan SK, Sacchettini JC, et al. Diflunisal analogues stabilize the native state of transthyretin. Potent inhibition of amyloidogenesis. J Med Chem. 2004;47:355–374.
   PubMed Web of Science ®Google Scholar
• Baures PW, Oza VB, Peterson SA, et al. Synthesis and evaluation of inhibitors of transthyretin amyloid formation based on the non-steroidal anti-inflammatory drug, flufenamic acid. Bioorg Med Chem. 1999;7:1339–1347.
   PubMed Web of Science ®Google Scholar
• Green NS, Palaninathan SK, Sacchettini JC, et al. Synthesis and characterization of potent bivalent amyloidosis inhibitors that bind prior to transthyretin tetramerization. J Am Chem Soc. 2003;125:13404–13414.
   PubMed Web of Science ®Google Scholar
• Oza VB, Petrassi HM, Purkey HE, et al. Synthesis and evaluation of anthranilic acid-based transthyretin amyloid fibril inhibitors. Bioorg Med Chem Lett. 1999;9:1–6.
   PubMed Web of Science ®Google Scholar
• Penchala SC, Connelly S, Wang Y, et al. AG10 inhibits amyloidogenesis and cellular toxicity of the familial amyloid cardiomyopathy-associated V122I transthyretin. Proc Natl Acad Sci USA. 2013;110:9992–9997.
   PubMed Web of Science ®Google Scholar
• Peterson SA, Klabunde T, Lashuel HA, et al. Inhibiting transthyretin conformational changes that lead to amyloid fibril formation. Proc Natl Acad Sci USA. 1998;95:12956–12960.
   PubMed Web of Science ®Google Scholar
• Purkey HE, Palaninathan SK, Kent KC, et al. Hydroxylated polychlorinated biphenyls selectively bind transthyretin in blood and inhibit amyloidogenesis: rationalizing rodent PCB toxicity. Chem Biol. 2004;11:1719–1728.
   PubMed Web of Science ®Google Scholar
• Razavi H, Palaninathan SK, Powers ET, et al. Benzoxazoles as transthyretin amyloid fibril inhibitors: synthesis, evaluation, and mechanism of action. Angew Chem Int Ed Engl. 2003;42:2758–2761.
   PubMed Web of Science ®Google Scholar
• Razavi H, Powers ET, Purkey HE, et al. Design, synthesis, and evaluation of oxazole transthyretin amyloidogenesis inhibitors. Bioorg Med Chem Lett. 2005;15:1075–1078.
   PubMed Web of Science ®Google Scholar
• Coelho T, Maia LF, da Silva AM, et al. Long-term effects of tafamidis for the treatment of transthyretin familial amyloid polyneuropathy. J Neurol. 2013;260:2802–2814.
   PubMed Web of Science ®Google Scholar
• Coelho T, Maia LF, Martins da Silva A, et al. Tafamidis for transthyretin familial amyloid polyneuropathy: a randomized, controlled trial. Neurology. 2012;79:785–792.
   PubMed Web of Science ®Google Scholar
• Berk JL, Suhr OB, Obici L, et al. Repurposing diflunisal for familial amyloid polyneuropathy: a randomized clinical trial. JAMA. 2013;310:2658–2667.
   PubMed Web of Science ®Google Scholar
• Epstein M. Non-steroidal anti-inflammatory drugs and the continuum of renal dysfunction. J Hypertens Suppl. 2002;20:S17–S23.
   PubMedGoogle Scholar
• Kearney PM, Baigent C, Godwin J, et al. Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials. BMJ. 2006;332:1302–1308.
   PubMed Web of Science ®Google Scholar
• Khan M, Fraser A. Cox-2 inhibitors and the risk of cardiovascular thrombotic events. Ir Med J. 2012;105:119–121.
   PubMedGoogle Scholar
• Mukherjee D, Nissen SE, Topol EJ. Risk of cardiovascular events associated with selective COX-2 inhibitors. JAMA. 2001;286:9549.
   Web of Science ®Google Scholar
• Peretto I, Radaelli S, Parini C, et al. Synthesis and biological activity of flurbiprofen analogues as selective inhibitors of beta-amyloid(1)(-)(42) secretion. J Med Chem. 2005;48:5705–5720.
   PubMed Web of Science ®Google Scholar
• Adams D, Samuel D, Goulon-Goeau C, et al. The course and prognostic factors of familial amyloid polyneuropathy after liver transplantation. Brain. 2000;123:1495–1504.
   PubMed Web of Science ®Google Scholar
• Cavallaro T, Martone RL, Dwork AJ, et al. The retinal pigment epithelium is the unique site of transthyretin synthesis in the rat eye. Invest Ophthalmol Vis Sci. 1990;31:497–501.
   PubMed Web of Science ®Google Scholar
• Suhr OB, Anan I, Ahlstrom KR, et al. Gastric emptying before and after liver transplantation for familial amyloidotic polyneuropathy, Portuguese type (Val30Met). Amyloid. 2003;10:121–126.
   PubMed Web of Science ®Google Scholar
• Nowak G, Suhr OB, Wikstrom L, et al. The long-term impact of liver transplantation on kidney function in familial amyloidotic polyneuropathy patients. Transpl Int. 2005;18:111–115.
   PubMed Web of Science ®Google Scholar
• Ohya Y, Okamoto S, Tasaki M, et al. Manifestations of transthyretin-related familial amyloidotic polyneuropathy: long-term follow-up of Japanese patients after liver transplantation. Surg Today. 2011;41:1211–1218.
   PubMed Web of Science ®Google Scholar
• Hornsten R, Wiklund U, Olofsson BO, et al. Liver transplantation does not prevent the development of life-threatening arrhythmia in familial amyloidotic polyneuropathy, Portuguese-type (ATTR Val30Met) patients. Transplantation. 2004;78:112–116.
   PubMed Web of Science ®Google Scholar
• Yamamoto S, Wilczek HE, Nowak G, et al. Liver transplantation for familial amyloidotic polyneuropathy (FAP): a single-center experience over 16 years. Am J Transplant. 2007;7:2597–2604.
   PubMed Web of Science ®Google Scholar
• Ihse E, Suhr OB, Hellman U, et al. Variation in amount of wild-type transthyretin in different fibril and tissue types in ATTR amyloidosis. J Mol Med. 2011;89:171–180.
   PubMed Web of Science ®Google Scholar
• Liepnieks JJ, Benson MD. Progression of cardiac amyloid deposition in hereditary transthyretin amyloidosis patients after liver transplantation. Amyloid. 2007;14:277–282.
   PubMed Web of Science ®Google Scholar
• Oshima T, Kawahara S, Ueda M, et al. Changes in pathological and biochemical findings of systemic tissue sites in familial amyloid polyneuropathy more than 10 years after liver transplantation. J Neurol Neurosurg Psychiatry. 2014;85:740–746.
   PubMed Web of Science ®Google Scholar
• Ando Y, Terazaki H, Nakamura M, et al. A different amyloid formation mechanism: de novo oculoleptomeningeal amyloid deposits after liver transplantation. Transplantation. 2004;77:345–349.
   PubMed Web of Science ®Google Scholar
• Imbimbo BP, Fernandez M, Giardino L, et al. Relationship between cerebrospinal fluid (CSH) biomarkers and congnitive performance of patieints with mild cognitive impairment (MCI) after long-term treatment with CHF5074. Alzheimers Dement. 2014;10:273.
   Google Scholar
• Ross J, Sharma S, Winston J, et al. CHF5074 reduces biomarkers of neuroinflammation in patients with mild cognitive impairment: a 12-week, double-blind, placebo-controlled study. Curr Alzheimer Res. 2013;10:742–753.
   PubMed Web of Science ®Google Scholar
• Ross J, Sharma SK, Chatterjee A, et al. Sustained cognitive benefit in patients with mild cognitive impairment (MCI) upon prolonged treatment with CHF5074. Alzheimers Dement. 2013;9:530.
   Google Scholar
• Hammarstrom P, Sekijima Y, White JT, et al. D18G transthyretin is monomeric, aggregation prone, and not detectable in plasma and cerebrospinal fluid: a prescription for central nervous system amyloidosis? Biochemistry. 2003;42:6656–6663.
   PubMed Web of Science ®Google Scholar