Itanapraced (CHF5074) is an orally bioactive gamma-secretase modulator and a nonsteroidal anti~inflammatory analogue. Itanapraced can reduce the secretion of Aβ42 and Aβ40 with IC50s of 3.6 and 18.4 μM respectively. Itanapraced inhibits oxygen glucose deprivation (OGD)-induced apoptosis in hippocampal neurons. Itanapraced may be used in Alzheimer's disease (AD) research.

Physicochemical Properties

Molecular Formula	C16H11CL2FO2
Molecular Weight	325.1604
Exact Mass	324.012
Elemental Analysis	C, 59.10; H, 3.41; Cl, 21.80; F, 5.84; O, 9.84
CAS #	749269-83-8
PubChem CID	9996409
Appearance	White to off-white solid powder
LogP	4.915
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	3
Heavy Atom Count	21
Complexity	413
Defined Atom Stereocenter Count	0
SMILES	OC(C1(CC1)C(C=C2)=CC(F)=C2C3=CC=C(Cl)C(Cl)=C3)=O
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)
Chemical Name	1-[4-(3,4-dichlorophenyl)-3-fluorophenyl]cyclopropane-1-carboxylic acid
Synonyms	CHF 5074; CHF-5074; CHF5074
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	The suspension of APPswe in human neuroastroma cells (H4swe) is inhibited by itanapraced (0.03-100 μM), with IC50 values of 3.6 and 18.4 μM for Aβ42 and Aβ40, respectively [1]. At doses up to 15, itanapraced (5-200 μM) quantitatively controls action potential. The IC50 value of itanapraced (0-1000 μM; 30 min) is 106 μM [2]. In HEK293swe cells, itanapraced (30-100 μM) suppresses Notch processing at quantitatively adjusted μM [1]. The fluorescence of hippocampal neuron cells caused by hypoxia switch (OGD) can be greatly reduced by itanapraced (1-10 μM) [2].
ln Vivo	Itanapraced (face; 375 ppm given to diet, 17 weeks) lowers Aβ42 and Aβ40 levels and brain plaque load in Tg2576 button mice [1].
Animal Protocol	Animal/Disease Models: Male and female Tg2576 transgenic mice expressing the Swedish mutant form of human APP (APPswe) [1] Doses: 375 ppm Route of Administration: Oral; 375 ppm in diet for 17 weeks Experimental Results: Aged Tg2576 mice Total brain Aβ42 and Aβ40 levels and brain plaque burden were diminished. It does not cause COX-mediated toxic effects in the gastrointestinal tract and does not cause Notch-mediated cell differentiation abnormalities in the ileum.
References	[1]. 1-(3',4'-Dichloro-2-fluoro[1,1'-biphenyl]-4-yl)-cyclopropanecarboxylic acid (CHF5074), a novel gamma-secretasemodulator, reduces brain beta-amyloid pathology in a transgenic mouse model of Alzheimer's disease withoutcausing peripheral toxicity. J Pharmacol Exp Ther. 2007 Dec;323(3):822-830. [2]. Electrophysiological and metabolic effects of CHF5074 in the hippocampus: protection against in vitro ischemia. Pharmacol Res. 2014 Mar;81:83-90.

Solubility Data

Solubility (In Vitro)

DMSO : ~100 mg/mL (~307.54 mM)

Solubility (In Vivo)

Solubility in Formulation 1: 2.5 mg/mL (7.69 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (7.69 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.0754 mL	15.3770 mL	30.7541 mL
	5 mM	0.6151 mL	3.0754 mL	6.1508 mL
	10 mM	0.3075 mL	1.5377 mL	3.0754 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.