| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Orvepitant Maleate targets the neurokinin-1 (NK1) receptor, a G-protein-coupled receptor that binds substance P. As a potent and selective NK1 receptor antagonist with a pKi of 10.2 for the human receptor, it blocks substance P-mediated signaling. NK1 receptor antagonism has been shown to produce antidepressant, anxiolytic, and antiemetic effects.
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| ln Vitro |
The capacity of orvepitant (Compound 3a) to functionally inhibit substance P (SP)-induced cytosolic Ca2+ release in human neurokinin-1 receptor (hNK1)-CHO cells was another way that the compound was identified. When orvitamin (0.3–10 nM) was added to the agonist SP after it had been preincubated for an hour at 37°C, the agonist concentration–response curve became insurmountably antagonistic. The apparent pKB value of Orvepitant is 10.30[1].
In vitro, Orvepitant Maleate acts as a potent and selective NK1 receptor antagonist with a pKi of 10.2 for the human neurokinin-1 receptor. It can cross the blood-brain barrier, enabling central nervous system activity. Its in vitro activity is assessed using receptor binding assays and functional assays measuring substance P-induced signaling in cells expressing the NK1 receptor. |
| ln Vivo |
The number of postures seen at 1 mg/kg (34.9% reduction), 3 mg/kg (36.6% reduction), and 10 mg/kg (46.4% reduction) demonstrated a dose-dependent way upon treatment with Ovitan (Compound 3a; 0.3-10 mg/kg; oral; marmoset), suggesting that the compound may have anxiolytic-like effects [1]. In rats, Ovitan (Compound 3a) has an oral bioavailability (F) of 17% and a plasma clearance (Clp) of 29 mL/min/kg in rats and 55% in dogs. 6 mL/min/kg is the medium. A dog can live for 6.1 hours, but a rat can live for 2.3 hours. Five minutes following an intravenous administration of a dose of 1 mg/kg of Orvepitant, a B/P value of 1.2 was noted in relation to rat brain penetration [1].
In vivo activity of Orvepitant Maleate has been demonstrated in preclinical models of depression, anxiety, and cough. As an orally active compound, it produces antidepressant- and anxiolytic-like effects. Its ability to cross the BBB enables its central nervous system effects. It has been clinically investigated for CINV, depression, anxiety, and PTSD. |
| Enzyme Assay |
The in vitro receptor binding assay for Orvepitant Maleate involves measuring its affinity for the NK1 receptor using radioligand binding techniques. These assays use membrane preparations from cells expressing the human NK1 receptor and measure the displacement of a labeled ligand by the compound. A pKi of 10.2 for the human NK1 receptor is determined, indicating high affinity. Selectivity over other neurokinin receptors is also assessed.
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| Cell Assay |
In vitro cellular assays for Orvepitant Maleate are performed using cells expressing the human NK1 receptor. These assays measure the compound's ability to antagonize substance P-induced signaling, such as calcium mobilization or inositol phosphate accumulation. The compound's potent and selective NK1 antagonism is demonstrated by its ability to inhibit substance P-mediated effects.
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| Animal Protocol |
Animal/Disease Models: Marmoset Human Threat Test (HTT) [1]
Doses: 0.3 mg/kg, 1 mg/kg, 3 mg/kg and 10 mg/kg Route of Administration: Oral Experimental Results: Dose-dependent reduction in quantity at 1 Posture was observed at mg/kg (34.9% reduction), 3 mg/kg (36.6% reduction), and 10 mg/kg (46.4% reduction). In vivo animal studies for Orvepitant Maleate are conducted in models of depression, anxiety, and cough. These studies typically involve oral administration of the compound, followed by assessment of behavioral endpoints such as forced swim test, elevated plus maze, or cough reflex. The compound's ability to cross the BBB and produce central nervous system effects is evaluated. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of Orvepitant Maleate are characterized by oral activity, bioavailability, and ability to cross the blood-brain barrier. As an orally active compound, it is designed for systemic administration and has favorable ADME properties. Its ability to cross the BBB enables its central nervous system effects. The compound's pharmacokinetic profile supports once-daily dosing.
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| Toxicity/Toxicokinetics |
Toxicology studies of Orvepitant Maleate have been conducted to support its clinical development. As an NK1 receptor antagonist, its toxicology profile includes effects on the central nervous system and gastrointestinal function. Preclinical toxicology studies include acute and repeat-dose toxicity assessments, as well as evaluations of CNS and GI safety. The compound is generally well-tolerated at therapeutic doses.
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| References |
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| Additional Infomation |
Orvepitant Maleate (GW823296 maleate) is a potent, selective, and orally active NK1 receptor antagonist with a pKi of 10.2 for the human receptor. It has been clinically investigated for the treatment of chemotherapy-induced nausea and vomiting (CINV), depression, anxiety, post-traumatic stress disorder (PTSD), and chronic refractory cough. Its ability to cross the BBB enables its central nervous system effects.
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| Molecular Formula |
C35H39F7N4O6
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|---|---|
| Molecular Weight |
744.71
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| Exact Mass |
744.276
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| CAS # |
579475-24-4
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| PubChem CID |
44225656
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
6.322
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
14
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
52
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| Complexity |
1140
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| Defined Atom Stereocenter Count |
4
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| SMILES |
CC1=C(C=CC(=C1)F)[C@H]2C[C@H](CCN2C(=O)N(C)[C@H](C)C3=CC(=CC(=C3)C(F)(F)F)C(F)(F)F)N4CCN5[C@H](C4)CCC5=O.C(=C\C(=O)O)\C(=O)O
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| InChi Key |
IPACOHTZCSBGBV-WUXDIRCFSA-N
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| InChi Code |
InChI=1S/C31H35F7N4O2.C4H4O4/c1-18-12-23(32)4-6-26(18)27-16-24(40-10-11-41-25(17-40)5-7-28(41)43)8-9-42(27)29(44)39(3)19(2)20-13-21(30(33,34)35)15-22(14-20)31(36,37)38;5-3(6)1-2-4(7)8/h4,6,12-15,19,24-25,27H,5,7-11,16-17H2,1-3H3;1-2H,(H,5,6)(H,7,8)/b;2-1-/t19-,24+,25+,27-;/m1./s1
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| Chemical Name |
(2R,4S)-4-[(8aS)-6-oxo-1,3,4,7,8,8a-hexahydropyrrolo[1,2-a]pyrazin-2-yl]-N-[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl]-2-(4-fluoro-2-methylphenyl)-N-methylpiperidine-1-carboxamide;(Z)-but-2-enedioic acid
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| Synonyms |
GW 823296B; GW823296B; GW-823296B
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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 : ~30 mg/mL (~40.28 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (6.71 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 50.0 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: ≥ 5 mg/mL (6.71 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 50.0 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. View More
Solubility in Formulation 3: ≥ 5 mg/mL (6.71 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.3428 mL | 6.7140 mL | 13.4280 mL | |
| 5 mM | 0.2686 mL | 1.3428 mL | 2.6856 mL | |
| 10 mM | 0.1343 mL | 0.6714 mL | 1.3428 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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