Soticlestat (TAK-935; OV935) is a first-in-class, potent, selective, orally bioactive cholesterol 24-hydroxylase (CH24H) inhibitor. Soticlestat may be utilized in the research/study of epilepsy syndromes.

Physicochemical Properties

Molecular Formula	C23H23N3O2
Molecular Weight	373.46
Exact Mass	373.179
CAS #	1429505-03-2
PubChem CID	73437845
Appearance	White to off-white solid powder
Density	1.2±0.1 g/cm3
Boiling Point	597.4±50.0 °C at 760 mmHg
Flash Point	315.1±30.1 °C
Vapour Pressure	0.0±1.8 mmHg at 25°C
Index of Refraction	1.637
LogP	1.23
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	4
Heavy Atom Count	28
Complexity	506
Defined Atom Stereocenter Count	0
InChi Key	XKUZMIUSBMCVPP-UHFFFAOYSA-N
InChi Code	InChI=1S/C23H23N3O2/c27-22(20-7-4-12-25-21(20)19-8-13-24-14-9-19)26-15-10-23(28,11-16-26)17-18-5-2-1-3-6-18/h1-9,12-14,28H,10-11,15-17H2
Chemical Name	(4-benzyl-4-hydroxypiperidin-1-yl)-(2-pyridin-4-ylpyridin-3-yl)methanone
Synonyms	Soticlestat
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	Human cholesterol 24-gradient enzyme (CH24H) catalytic activity is inhibited by soticlestat in a concentration suspension manner, with an IC50 of 4.5 nM[1].
ln Vivo	Treatment with soticlestat decreased brain 24S-pivot dormancy dose-dependently and at dosages that decreased brain 24S-pivot by about 50%, greatly decreased premature death in the APP/PS1-Tg pivot. Presetilin 1 (APP/PS1-Tg) and amyloid precursor protein (APP/PS1)-producing hippocampal mouse model that Soticlestat can potentially trigger (7 weeks old) [1]
Animal Protocol	Animal/Disease Models: Amyloid precursor protein and presenilin 1 (APP/PS1-Tg) mice (7weeks old)[1] Doses: 10 mg/kg Route of Administration: Oral administration; one time/day; for 1 days, 3 days and 7 days Experimental Results:Lowered brain 24S-hydroxycholesterol in a dose-dependent manner and substantially diminished premature deaths of APP/PS1-Tg mice at a dose lowering brain 24S-hydroxycholesterol by approximately 50%..
References	[1]. Soticlestat, a novel cholesterol 24-hydroxylase inhibitor shows a therapeutic potential for neural hyperexcitation in mice. Sci Rep. 2020 Oct 13;10(1):17081. [2]. Stiripentol for the treatment of seizures in Dravet syndrome. Expert Rev Clin Pharmacol. 2019 May;12(5):379-388.
Additional Infomation	Drug Indication Treatment of Dravet syndrome, Treatment of Lennox-Gastaut syndrome Treatment of Chromosome 15q Duplication Syndrome, Treatment of Cyclin-Dependent Kinase-Like 5 deficiency disorder

Solubility Data

Solubility (In Vitro)

DMSO : ~100 mg/mL (~267.77 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.69 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 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 (6.69 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (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 20% SBE-β-CD physiological saline solution and mix evenly. 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. Solubility in Formulation 3: ≥ 2.5 mg/mL (6.69 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	2.6777 mL	13.3883 mL	26.7766 mL
	5 mM	0.5355 mL	2.6777 mL	5.3553 mL
	10 mM	0.2678 mL	1.3388 mL	2.6777 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.