ARN14494 is a potent and specific serine palmitoyltransferase (SPT) inhibitor (antagonist) with IC50 of 27.3 nM. ARN14494 affects the central nervous system/CNS in anti-inflammatory and neuro-protection aspects. ARN14494 protects neurons from β-amyloid 1-42-induced neurotoxicity through multiple mechanisms such as antioxidant, anti-apoptosis, and anti-inflammation. ARN14494 could be used in AD/Alzheimer's disease study.

Physicochemical Properties

Molecular Formula	C24H32N4O3
Molecular Weight	424.54
Exact Mass	424.247
CAS #	1037837-27-6
Related CAS #	1037837-27-6 ;1037834-43-7;
PubChem CID	59846699
Appearance	Typically exists as solid at room temperature
LogP	1.7
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	4
Heavy Atom Count	31
Complexity	708
Defined Atom Stereocenter Count	0
InChi Key	TYZOOEYUTZDYPB-UHFFFAOYSA-N
InChi Code	InChI=1S/C24H32N4O3/c1-25-24(31)16-5-6-21-19(11-16)12-22(29)28(21)20-7-9-26(10-8-20)15-23(30)27-13-17-3-2-4-18(17)14-27/h5-6,11,17-18,20H,2-4,7-10,12-15H2,1H3,(H,25,31)
Chemical Name	1-[1-[2-(3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl)-2-oxoethyl]piperidin-4-yl]-N-methyl-2-oxo-3H-indole-5-carboxamide
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

Targets	IL-1β iNOS COX-2
ln Vitro	In a concentration-dependent manner, ARN14494 (1-10 μM) suppresses the SPT activity of primary mouse astrocytes [1]. Ceramide and dihydroceramide levels in cerebral cortical astrocytes are lowered by ARN14494 (10 μM, 24 h) when it is produced by Aβ1-42 [1]. ARN14494 (10 μM, 0-24 h) suppresses pro-inflammatory chemicals (NO, TNF-α, IL1β, TGF1β, pro-inflammatory enzymes INOS and COX-2) generated by oligomeric Aβ in primary astrocyte cultures Produce[1]. Relevance of ARN14494 on caspase-3 activation and Aβ neurotoxicity in cortical neurons [1].
References	[1]. Inhibition of Serine Palmitoyltransferase by a Small Organic Molecule Promotes Neuronal Survival after Astrocyte Amyloid Beta 1-42 Injury. ACS Chem Neurosci. 2019 Mar 20;10(3):1627-1635.

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	2.3555 mL	11.7775 mL	23.5549 mL
	5 mM	0.4711 mL	2.3555 mL	4.7110 mL
	10 mM	0.2355 mL	1.1777 mL	2.3555 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.