CHF5074

• CAT Number: I004782
• CAS Number: 749269-83-8
• Molecular Formula: C16H11Cl2FO2
• Molecular Weight: 325.16
• Purity: ≥95%
• Target: γ-secretase
• Solubility: DMSO: ≥ 37 mg/mL
• Storage: Store at -20°C
• IC50: 3.6 μM (Aβ42), 18.4 μM (Aβ40) [1]
• InChI: InChI=1S/C16H11Cl2FO2/c17-12-4-1-9(7-13(12)18)11-3-2-10(8-14(11)19)16(5-6-16)15(20)21/h1-4,7-8H,5-6H2,(H,20,21)
• InChIKey: LIYLTQQDABRNRX-UHFFFAOYSA-N
• SMILES: O=C(C1(C2=CC=C(C3=CC=C(Cl)C(Cl)=C3)C(F)=C2)CC1)O

CHF5074 (CAT: I004782) is a novel γ-secretase modulator. It is a small molecule compound that modulates the activity of the γ-secretase enzyme, which plays a crucial role in the processing of amyloid precursor protein (APP) and the generation of amyloid beta (Aβ) peptides. CHF5074 has been studied for its potential therapeutic application in neurodegenerative diseases, particularly Alzheimer’s disease. By modulating γ-secretase activity, CHF5074 aims to influence the production and aggregation of Aβ peptides, which are believed to contribute to the pathogenesis of Alzheimer’s disease. The modulation of γ-secretase by CHF5074 offers a potential avenue for the development of novel treatments for neurodegenerative disorders.

Reference

1:CSP-1103 (CHF5074) stabilizes human transthyretin in healthy human subjects. Qiang L, Guan Y, Li X, Liu L, Mu Y, Sugano A, Takaoka Y, Sakaeda T, Imbimbo BP, Yamamura KI, Jin S, Li Z.Amyloid. 2017 Apr 10:1-10. doi: 10.1080/13506129.2017.1308348. [Epub ahead of print] PMID: 28393633 2:CHF5074 (CSP-1103) stabilizes human transthyretin in mice humanized at the transthyretin and retinol-binding protein loci. Mu Y, Jin S, Shen J, Sugano A, Takaoka Y, Qiang L, Imbimbo BP, Yamamura K, Li Z.FEBS Lett. 2015 Mar 24;589(7):849-56. doi: 10.1016/j.febslet.2015.02.020. Epub 2015 Feb 26. PMID: 25728271 Free Article3:CHF5074 (CSP-1103) induces microglia alternative activation in plaque-free Tg2576 mice and primary glial cultures exposed to beta-amyloid. Porrini V, Lanzillotta A, Branca C, Benarese M, Parrella E, Lorenzini L, Calzà L, Flaibani R, Spano PF, Imbimbo BP, Pizzi M.Neuroscience. 2015 Aug 27;302:112-20. doi: 10.1016/j.neuroscience.2014.10.029. Epub 2014 Oct 22. PMID: 25450955 4:CHF5074 protects SH-SY5Y human neuronal-like cells from amyloidbeta 25-35 and tumor necrosis factor related apoptosis inducing ligand toxicity in vitro. Ronsisvalle N, Di Benedetto G, Parenti C, Amoroso S, Bernardini R, Cantarella G.Curr Alzheimer Res. 2014;11(7):714-24. PMID: 24938499 5:Electrophysiological and metabolic effects of CHF5074 in the hippocampus: protection against in vitro ischemia. Mango D, Barbato G, Piccirilli S, Panico MB, Feligioni M, Schepisi C, Graziani M, Porrini V, Benarese M, Lanzillotta A, Pizzi M, Pieraccini S, Sironi M, Blandini F, Nicoletti F, Mercuri NB, Imbimbo BP, Nisticò R.Pharmacol Res. 2014 Mar;81:83-90. doi: 10.1016/j.phrs.2014.02.010. Epub 2014 Mar 12. PMID: 24630950 6:CHF5074 and LY450139 sub-acute treatments differently affect cortical extracellular glutamate levels in pre-plaque Tg2576 mice. Beggiato S, Giuliani A, Sivilia S, Lorenzini L, Antonelli T, Imbimbo BP, Giardino L, Calzà L, Ferraro L.Neuroscience. 2014 Apr 25;266:13-22. doi: 10.1016/j.neuroscience.2014.01.065. Epub 2014 Feb 12. PMID: 24530449 7:CHF5074 reduces biomarkers of neuroinflammation in patients with mild cognitive impairment: a 12-week, double-blind, placebo-controlled study. Ross J, Sharma S, Winston J, Nunez M, Bottini G, Franceschi M, Scarpini E, Frigerio E, Fiorentini F, Fernandez M, Sivilia S, Giardino L, Calza L, Norris D, Cicirello H, Casula D, Imbimbo BP.Curr Alzheimer Res. 2013 Sep;10(7):742-53. PMID: 23968157 8:CHF5074 Reduces Biomarkers of Neuroinflammation in Patients with Mild Cognitive Impairment: A 12-Week, Double-Blind, Placebo-Controlled Study. Ross J, Sharma S, Winston J, Nunez M, Bottini G, Franceschi M, Scarpini E, Frigerio E, Fiorentini F, Fernandez M, Sivilia S, Giardin L, Calzà L, Norris D, Cicirello H, Casula D, Imbimbo B.Curr Alzheimer Res. 2013 Aug 2. [Epub ahead of print] PMID: 23952019 9:Multi-target action of the novel anti-Alzheimer compound CHF5074: in vivo study of long term treatment in Tg2576 mice. Sivilia S, Lorenzini L, Giuliani A, Gusciglio M, Fernandez M, Baldassarro VA, Mangano C, Ferraro L, Pietrini V, Baroc MF, Viscomi AR, Ottonello S, Villetti G, Imbimbo BP, Calzà L, Giardino L.BMC Neurosci. 2013 Apr 5;14:44. doi: 10.1186/1471-2202-14-44. PMID: 23560952 Free PMC Article10:CHF5074 restores visual memory ability and pre-synaptic cortical acetylcholine release in pre-plaque Tg2576 mice. Giuliani A, Beggiato S, Baldassarro VA, Mangano C, Giardino L, Imbimbo BP, Antonelli T, Calzà L, Ferraro L.J Neurochem. 2013 Mar;124(5):613-20. doi: 10.1111/jnc.12136. Epub 2013 Jan 28. PMID: 23278303 Free Article