Synonym
CHF-5074; CHF5074; CHF 5074; CSP-1103; CSP 1103; CSP1103; Itanapraced
IUPAC/Chemical Name
1-[4-(3,4-dichlorophenyl)-3-fluorophenyl]cyclopropane-1-carboxylic acid
InChi Key
LIYLTQQDABRNRX-UHFFFAOYSA-N
InChi Code
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)
SMILES Code
O=C(C1(C2=CC=C(C3=CC=C(Cl)C(Cl)=C3)C(F)=C2)CC1)O
Purity
>97% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
Itanapraced (CHF5074) is a novel γ-secretase modulator, reduces Aβ42 and Aβ40 secretion, with an IC50 of 3.6 and 18.4 μM, respectively.
In vitro activity:
Here, the effects of CHF5074 on Aβ25-35- triggered TRAIL toxicity were evaluated in the differentiated human neuroblastoma cell line SH-SY5Y in vitro. Cells were pre-treated 1h with CHF5074 at graded concentrations (range: 1 nM-1 uM) and then challenged for 72 h with either Aβ25-35 or TRAIL. Results show that CHF5074 treatment prevented apoptotic death in SH-SY5Y cell line in a concentration- dependent fashion. Its maximally active concentration was 10 nM. Then, investigation of related molecular mechanisms underlying such protective effect of CHF5074 suggested that the levels of caspases, as well as of various kinases, including stress and MAP kinases, are modulated by CHF5074. Finally, treatment of injured human neuroblastoma cell line SH-SY5Y with CHF5074 resulted in prominent protection from apoptotic death. The bulk of these data suggest that CHF5074 represents a potential candidate for pharmacological neuroprotective treatment in neurodegenerative disorders.
Reference: Curr Alzheimer Res. 2014;11(7):714-24. https://www.eurekaselect.com/122812/article
In vivo activity:
Compared with transgenic controls, CHF5074 treatment significantly reduced the area occupied by plaques in cortex (P = 0.003) and hippocampus (P = 0.004). The number of plaques were also reduced by CHF5074 in both cortex (P = 0.022) and hippocampus (P = 0.005). Plaque-associated microglia in CHF5074-treated animals was lower than in transgenic controls in cortex (P = 0.008) and hippocampus (P = 0.002). Ibuprofen treatment significantly reduced microglia area in cortex and hippocampus but not beta-amyloid burden. On the last day of the Morris water maze, transgenic controls performed significantly worse than the non-transgenic animals and the CHF5074-treated transgenic mice, on the swimming path to reach the hidden platform. Ibuprofen-treated animals did not perform significantly better than transgenic controls.
Reference: Br J Pharmacol. 2009 Mar;156(6):982-93. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19239474/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
59.0 |
181.45 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
325.16
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
In vitro protocol:
1. Ronsisvalle N, Di Benedetto G, Parenti C, Amoroso S, Bernardini R, Cantarella G. CHF5074 protects SH-SY5Y human neuronal-like cells from amyloidbeta 25-35 and tumor necrosis factor related apoptosis inducing ligand toxicity in vitro. Curr Alzheimer Res. 2014;11(7):714-24. doi: 10.2174/1567205011666140618104430. PMID: 24938499.
2. 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. Electrophysiological and metabolic effects of CHF5074 in the hippocampus: protection against in vitro ischemia. Pharmacol Res. 2014 Mar;81:83-90. doi: 10.1016/j.phrs.2014.02.010. Epub 2014 Mar 12. PMID: 24630950.
In vivo protocol:
1. Imbimbo BP, Hutter-Paier B, Villetti G, Facchinetti F, Cenacchi V, Volta R, Lanzillotta A, Pizzi M, Windisch M. 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 Mar;156(6):982-93. doi: 10.1111/j.1476-5381.2008.00097.x. PMID: 19239474; PMCID: PMC2697723.
2. Giuliani A, Beggiato S, Baldassarro VA, Mangano C, Giardino L, Imbimbo BP, Antonelli T, Calzà L, Ferraro L. CHF5074 restores visual memory ability and pre-synaptic cortical acetylcholine release in pre-plaque Tg2576 mice. J Neurochem. 2013 Mar;124(5):613-20. doi: 10.1111/jnc.12136. Epub 2013 Jan 28. PMID: 23278303.
1: Mu Y, Jin S, Shen J, Sugano A, Takaoka Y, Qiang L, Imbimbo BP, Yamamura K, Li Z. CHF5074 (CSP-1103) stabilizes human transthyretin in mice humanized at the transthyretin and retinol-binding protein loci. FEBS Lett. 2015 Mar 24;589(7):849-56. doi: 10.1016/j.febslet.2015.02.020. PubMed PMID: 25728271.
2: Porrini V, Lanzillotta A, Branca C, Benarese M, Parrella E, Lorenzini L, Calzà L, Flaibani R, Spano PF, Imbimbo BP, Pizzi M. CHF5074 (CSP-1103) induces microglia alternative activation in plaque-free Tg2576 mice and primary glial cultures exposed to beta-amyloid. Neuroscience. 2015 Aug 27;302:112-20. doi: 10.1016/j.neuroscience.2014.10.029. PubMed PMID: 25450955.
3: Ronsisvalle N, Di Benedetto G, Parenti C, Amoroso S, Bernardini R, Cantarella G. CHF5074 protects SH-SY5Y human neuronal-like cells from amyloidbeta 25-35 and tumor necrosis factor related apoptosis inducing ligand toxicity in vitro. Curr Alzheimer Res. 2014;11(7):714-24. PubMed PMID: 24938499.
4: Branca C, Sarnico I, Ruotolo R, Lanzillotta A, Viscomi AR, Benarese M, Porrini V, Lorenzini L, Calzà L, Imbimbo BP, Ottonello S, Pizzi M. Pharmacological targeting of the β-amyloid precursor protein intracellular domain. Sci Rep. 2014 Apr 9;4:4618. doi: 10.1038/srep04618. PubMed PMID: 24714650; PubMed Central PMCID: PMC3980230.
