| Identification | Back Directory | [Name]
ACT-335827 | [CAS]
1354039-86-3 | [Synonyms]
ACT-335827
ACT 335827; ACT335827
ACT-335827,CID 54765113
(aR,1S)-1-[(3,4-Dimethoxyphenyl)methyl]-3,4-dihydro-6,7-dimethoxy-N-(1-methylethyl)-a-phenyl-2(1H)-isoquinolineacetamide
(2R)-2-[(1S)-1-[(3,4-dimethoxyphenyl)methyl]-6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl]-N-isopropyl-2-phenyl-acetamide
(2R)-2-[(1S)-1-[(3,4-DIMETHOXYPHENYL)METHYL]-6,7-DIMETHOXY-3,4-DIHYDRO-1H-ISOQUINOLIN-2-YL]-2-PHENYL-N-PROPAN-2-YLACETAMIDE | [Molecular Formula]
C31H38N2O5 | [MDL Number]
MFCD27991288 | [MOL File]
1354039-86-3.mol | [Molecular Weight]
518.65 |
| Chemical Properties | Back Directory | [Boiling point ]
664.0±55.0 °C(Predicted) | [density ]
1.144±0.06 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
<51.86mg/ml in DMSO; <51.86mg/ml in ethanol | [form ]
solid | [pka]
14.75±0.46(Predicted) | [color ]
Off-white |
| Hazard Information | Back Directory | [Uses]
ACT 335827 is an orally available, brain penetrant orexin receptor type 1 selective antagonist and elicits anxiolytic-like effects without promoting sleep. | [Biological Activity]
act 335827 is a potent and selective antagonist of oxr-1 with ic50 values of 120 and 2300 nm for oxr-1 and oxr-2, respectively [1].orexin receptor 1 (oxr-1) is a g-protein coupled receptor for neuropeptide orexin-a and regulates feeding behaviour. oxr-1 is expressed in the hypothalamus.act 335827 is a potent and selective oxr-1 antagonist with kb values of 41 and 560 nm for oxr-1 and oxr-2, respectively [1].in the fear-potentiated startle rats, act-335827 (300 mg/kg) inhibited fear-induced startle reactions. also, act-335827 (300 mg/kg) significantly reduced stress-induced tachycardia and hyperthermia. in the rat polydipsia model, act-335827 (300 mg/kg) inhibited compulsive drinking behavior [1]. in rats exposed to novelty stress, act-335827 (100 mg/kg) reduced the tachycardic and pressor by 48% and 32%, respectively [2]. in a diet-induced obesity(dio) rat model, act-335827 increased the level of high-density lipoprotein and water intake. also, it slightly increased body weight, which suggested that inhibition of oxr-1 had minimal impact in this model [3]. | [Enzyme inhibitor]
This brain-penetrant and orally available orexin receptor antagonist (FW = 518.64 g/mol; CAS 1354039-86-3; Soluble to 100 mM in DMSO, also known as (aR,1S)-1-[(3,4-Dimethoxyphenyl)methyl]-3,4-dihydro-6,7dimethoxy-N-(1-methylethyl)-a-phenyl-2(1H)-isoquinoline acetamide, elicits its anxiolytic effects in vivo by targeting OX1 (Ki = 41 nM) and OX2 (Ki = 560 nM) receptors. ACT-335827 decreases fear, compulsive behaviors, and autonomic stress reactions in rats. | [in vivo]
ACT-335827 (oral gavage, 30-100 mg/kg, once) can reduce the fear-induced startle response with no affecting motor or cognitive function in rats[1].
ACT-335827 (oral administration, 300 mg/kg, everyday, 4 weeks) has less effect on metabolic syndrome (MetS), such as diet-induced obesity (DIO) in male Wistar rats[2].
| Animal Model: | Rats[1] | | Dosage: | 30, 100 or 300 mg/kg | | Administration: | Oral gavage; once | | Result: | Reduced fear-induced startle response at 300 mg/kg.
Decreased stress-induced elevated body temperature at 300 mg/kg and accelerated heat rate at 100 or 300 mg/kg but no effect on locomotion and blood pressure.
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| Animal Model: | Male Wistar rats weighing160-180g[2] | | Dosage: | 300 mg/kg | | Administration: | Oral administration; everyday; 4 weeks | | Result: | Reduced preference for high fat/sweet diets but no effect on absolute energy intake.
Increased water intake and HDL relative to total cholesterol.
Resulted in a 4% weight gain compared to the control group.
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| [IC 50]
OX1: 6 nM (IC50); OX2: 417 nM (IC50) | [storage]
Store at -20°C | [References]
[1]. steiner ma, gatfield j, brisbare-roch c, et al. discovery and characterization of act-335827, an orally available, brain penetrant orexin receptor type 1 selective antagonist. chemmedchem, 2013, 8(6): 898-903.
[2]. beig mi, dampney bw, carrive p. both ox1r and ox2r orexin receptors contribute to the cardiovascular and locomotor components of the novelty stress response in the rat. neuropharmacology, 2015, 89: 146-156.
[3]. steiner ma, sciarretta c, pasquali a, et al. the selective orexin receptor 1 antagonist act-335827 in a rat model of diet-induced obesity associated with metabolic syndrome. front pharmacol, 2013, 4: 165. |
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BOC Sciences
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| Website: |
https://www.bocsci.com |
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