ELN318463 racemate is the racemate of ELN318463. ELN318463 is an amyloid precursor protein (APP)-selective γ-secretase inhibitor. ELN318463 has different inhibitory activities against γ-secretase containing progerin (PS1) and PS2, with EC50 of 12 nM and 656 nM for PS1 and PS2, respectively. ELN318463 is about 51 times more selective for PS1 than for PS2.

Physicochemical Properties

Molecular Formula	C19H20BRCLN2O3S
Molecular Weight	471.795701980591
Exact Mass	470.006
CAS #	851599-82-1
Related CAS #	ELN318463;851600-86-7
PubChem CID	18455200
Appearance	Typically exists as solid at room temperature
LogP	4.1
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	5
Heavy Atom Count	27
Complexity	597
Defined Atom Stereocenter Count	0
InChi Key	KTCJYACFOQWRDO-UHFFFAOYSA-N
InChi Code	InChI=1S/C19H20BrClN2O3S/c20-15-6-4-14(5-7-15)13-23(18-3-1-2-12-22-19(18)24)27(25,26)17-10-8-16(21)9-11-17/h4-11,18H,1-3,12-13H2,(H,22,24)
Chemical Name	N-[(4-bromophenyl)methyl]-4-chloro-N-(2-oxoazepan-3-yl)benzenesulfonamide
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	ELN318463 is a conventional gamma-secretase inhibitor that displaces active site-directed inhibitors only in the presence of substrate at very high concentrations and suppresses Aβ synthesis in cells 75–120 times more specifically than Notch signaling [2].
ln Vivo	ELN318463 was found in the brains of FVB and PDAPP subjects at 30 mg/kg and 100 mg/kg doses, respectively, with 0.754 μM and 0.69 μM in FVB brains and 1.87 μM and 2.7 μM in CPP brains, respectively. In BACE KO or wild-type BACE inhibitor-treated mice, discrepancies between Aβ1-40 and Aβx-40 have been documented [1].
References	[1]. Identification of gamma-secretase inhibitor potency determinants on presenilin. J Biol Chem. 2008 Feb 1;283(5):2927-38. [2]. Amyloid precursor protein selective gamma-secretase inhibitors for treatment of Alzheimer's disease. Alzheimers Res Ther. 2010 Dec 29;2(6):36.

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.1195 mL	10.5977 mL	21.1954 mL
	5 mM	0.4239 mL	2.1195 mL	4.2391 mL
	10 mM	0.2120 mL	1.0598 mL	2.1195 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.