ACT-335827 is a selective, orally bioactive, BBB (blood-brain barrier) permeable/penetrable orexin type 1 receptor blocker (antagonist). The IC50s of ACT-33582 for OXR1 and OXR2 are 6 nM and 417 nM, respectively. ACT-33582 can be used for research related to neurological diseases.

Physicochemical Properties

Molecular Formula	C31H38N2O5
Molecular Weight	518.65
Exact Mass	518.278
CAS #	1354039-86-3
PubChem CID	54765113
Appearance	Off-white to light yellow solid powder
LogP	5.457
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	10
Heavy Atom Count	38
Complexity	729
Defined Atom Stereocenter Count	2
SMILES	CC(C)NC(=O)[C@@H](C1=CC=CC=C1)N2CCC3=CC(=C(C=C3[C@@H]2CC4=CC(=C(C=C4)OC)OC)OC)OC
InChi Key	HXHOBPVRRPCTLG-SETSBSEESA-N
InChi Code	InChI=1S/C31H38N2O5/c1-20(2)32-31(34)30(22-10-8-7-9-11-22)33-15-14-23-18-28(37-5)29(38-6)19-24(23)25(33)16-21-12-13-26(35-3)27(17-21)36-4/h7-13,17-20,25,30H,14-16H2,1-6H3,(H,32,34)/t25-,30+/m0/s1
Chemical Name	(R)-2-((S)-1-(3,4-dimethoxybenzyl)-6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)-N-isopropyl-2-phenylacetamide
Synonyms	ACT-335827 ACT335827 ACT 335827
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	In CHO cells, ACT-335827 (0-10 μM, 2 h) acts on OXR-1 and OXR-2, with IC50 values of 2300 nM and 41 nM, respectively, and Kb values of 41 nM and 560 nM [1].
ln Vivo	Rats' startle reactions can be lessened by ACT-335827 (oral gavage, 30-100 mg/kg once), without impairing their motor or cognitive abilities [1]. Diet-induced obesity (DIO) in male Wistar rats is one metabolic syndrome (MetS) condition that ACT-335827 (oral, 300 mg/kg, daily, 4 weeks) has less of an impact on [2].
Animal Protocol	Animal/Disease Models: Rat[1] Doses: 30, 100 or 300 mg/kg Route of Administration: po (oral gavage); Experimental Results: At the dose of 300 mg/kg, the startle response caused by fear was diminished. At 300 mg/kg, it can reduce the increase in body temperature caused by stress, and at 100 or 300 mg/kg, it can accelerate the fever rate, but has no effect on exercise and blood pressure. Animal/Disease Models: Male Wistar rat, weight 160-180g[2] Doses: 300mg/kg Route of Administration: po (po (oral gavage)) 200mg/kg. Daily; 4 weeks Experimental Results: diminished preference for high-fat/sweet diets but no effect on absolute energy intake. Water intake and HDL content increased relative to total cholesterol. Compared with the control group, body weight increased by 4%.
References	[1]. Discovery and characterization of ACT-335827, an orally available, brain penetrant orexin receptor type 1 selective antagonist. ChemMedChem. 2013 Jun;8(6):898-903. [2]. The selective orexin receptor 1 antagonist ACT-335827 in a rat model of diet-induced obesity associated with metabolic syndrome. Front Pharmacol. 2013 Dec 30;4:165.

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	1.9281 mL	9.6404 mL	19.2808 mL
	5 mM	0.3856 mL	1.9281 mL	3.8562 mL
	10 mM	0.1928 mL	0.9640 mL	1.9281 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.