| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
Orexin-1 receptor (OX1R); Ki values are 16 nM for human OX1R and 700 nM for human OX2R, demonstrating high selectivity for OX1R over OX2R.
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|---|---|
| ln Vitro |
JNJ-54717793 exhibits high affinity for OX1R with a Ki of 16 nM in radioligand binding assays using membrane preparations from cells expressing human OX1R. It shows >40-fold selectivity over OX2R (Ki = 700 nM). In functional assays, it antagonizes orexin-A-induced calcium mobilization with potent activity.
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| ln Vivo |
Rapid eye movement (REM) sleep is known to have a significantly shorter latency and a longer duration when JNJ-5471779 (30 mg/kg; oral; 6 hours) is taken [2]. Orally administered JNJ-5471779 (3~30 mg/kg) can reduce the bradycardia response [2]. Low clearance is seen with JNJ-5471779 (5 mg/kg; oral) [1].
In rat models of panic attack provocation, JNJ-54717793 demonstrates anxiolytic and anti-addictive properties. It reduces stress-induced hyperthermia and blocks panic-like responses in the elevated plus maze and social interaction tests. The compound shows efficacy in models relevant to anxiety disorders. |
| Enzyme Assay |
Radioligand binding assay: Membranes from CHO-K1 cells expressing human OX1R or OX2R are incubated with [3H]EMPA (0.2 nM) and varying concentrations of JNJ-54717793 (0.01-10,000 nM) in 50 mM Tris-HCl buffer (pH 7.4) for 2 hours at 25degC. Bound radioactivity is collected on GF/B filters and counted by scintillation. Ki values are calculated using the Cheng-Prusoff equation.
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| Cell Assay |
Calcium mobilization assay: CHO-K1 cells expressing human OX1R are loaded with Fluo-4 AM dye and incubated with JNJ-54717793 (0.1-1000 nM) for 30 minutes. Cells are then stimulated with 10 nM orexin-A, and intracellular calcium flux is measured using a FLIPR or plate reader with 485/525 nm excitation/emission. IC50 for antagonist activity is calculated.
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| Animal Protocol |
Animal/Disease Models: OX2R KO mice [2]
Doses: 30 mg/kg Route of Administration: Po Experimental Results: Dramatically shortened the latency of rapid eye movement (REM) sleep and prolonged the duration of REM sleep. Animal/Disease Models: Rat[2] Doses: 3~30 mg/kg Route of Administration: Oral Experimental Results:The bradycardia response was weakened. Animal/Disease Models: Mouse[1] Doses: 5.0 mg/kg (pharmacokinetic/PK/PK analysis) Route of Administration: Po Experimental Results: The clearance rate was found to be low. Rat panic model: Male Sprague-Dawley rats are administered JNJ-54717793 orally (1-30 mg/kg) or vehicle 60 minutes prior to testing. In the panic provocation test, rats are exposed to a predator odor (cat fur) or CO2 challenge; panic-like behaviors (freezing, escape attempts) are scored. Plasma samples are collected at endpoint for compound concentration measurement. |
| ADME/Pharmacokinetics |
Rat oral PK: Following oral administration (10 mg/kg), Cmax is achieved at 1-2 hours, with a plasma EC50 of 85 ng/mL. The compound shows good oral bioavailability (>50%) and brain penetration (brain/plasma ratio ~0.5). Terminal half-life is approximately 3-5 hours in rats. Metabolism is primarily hepatic via CYP450 enzymes.
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| Toxicity/Toxicokinetics |
In preclinical studies, JNJ-54717793 is well-tolerated at therapeutic doses. No significant adverse effects on motor function, cardiovascular parameters, or body weight are reported. At high doses (>100 mg/kg), mild sedation and reduced locomotor activity may occur due to OX1R antagonism. Formal toxicology studies are not publicly disclosed.
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| References |
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| Additional Infomation |
JNJ-54717793 is a research compound developed by Johnson & Johnson, described in ACS Med Chem Lett (2020) and evaluated in rat panic models (Front Pharmacol, 2017). It is not FDA-approved but serves as a valuable tool for studying the orexin system's role in anxiety, addiction, and stress-related disorders.
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| Molecular Formula |
C22H18F4N6O
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|---|---|
| Molecular Weight |
458.411537647247
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| Exact Mass |
458.147
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| CAS # |
1628843-99-1
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| PubChem CID |
90412187
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| Appearance |
Off-white to pink solid powder
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| LogP |
3
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
33
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| Complexity |
705
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| Defined Atom Stereocenter Count |
3
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| SMILES |
FC1C=CC=C(C=1C1N=CC=CN=1)C(N1[C@@H]2CC[C@H]1[C@@H](C2)NC1C=NC(C(F)(F)F)=CN=1)=O
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| InChi Key |
NWUAUSABGZEYEW-WQVCFCJDSA-N
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| InChi Code |
InChI=1S/C22H18F4N6O/c23-14-4-1-3-13(19(14)20-27-7-2-8-28-20)21(33)32-12-5-6-16(32)15(9-12)31-18-11-29-17(10-30-18)22(24,25)26/h1-4,7-8,10-12,15-16H,5-6,9H2,(H,30,31)/t12-,15-,16+/m1/s1
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| Chemical Name |
(3-fluoro-2-pyrimidin-2-ylphenyl)-[(1S,2R,4R)-2-[[5-(trifluoromethyl)pyrazin-2-yl]amino]-7-azabicyclo[2.2.1]heptan-7-yl]methanone
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO : ~240 mg/mL (~523.55 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 6 mg/mL (13.09 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 60.0 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: ≥ 6 mg/mL (13.09 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 60.0 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1815 mL | 10.9073 mL | 21.8145 mL | |
| 5 mM | 0.4363 mL | 2.1815 mL | 4.3629 mL | |
| 10 mM | 0.2181 mL | 1.0907 mL | 2.1815 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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