| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
Neurokinin-1 (NK1) receptor (TACR1, tachykinin receptor 1). Orvepitant competitively antagonizes the NK1 receptor, blocking the binding of substance P. NK1 receptor is a G-protein coupled receptor that mediates the effects of substance P in the central nervous system, including modulation of mood, anxiety, and emesis.
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|---|---|
| ln Vitro |
Orvepitant is a highly potent and selective NK1 receptor antagonist. It blocks substance P-mediated signaling at the NK1 receptor. It is orally active and has been evaluated in clinical trials for major depressive disorder, anxiety, and insomnia. It also demonstrates efficacy in inhibiting EGFRI-induced pruritus. Specific binding affinity and functional potency data are reported in the scientific literature.
|
| ln Vivo |
In vivo, orvepitant has been evaluated in Phase 2 clinical trials for chronic refractory cough and in Phase 1 trials for depression and anxiety. It is well-tolerated and has good oral bioavailability. It inhibits EGFRI-induced pruritus in animal models. Its pharmacokinetics, safety, and tolerability have been assessed in healthy volunteers using oral formulations.
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| Enzyme Assay |
Radioligand binding assays use membranes from cells expressing recombinant human NK1 receptors. [125I]-Substance P or a selective NK1 radioligand is used. Orvepitant is added at increasing concentrations to compete for binding. Nonspecific binding is determined with excess unlabeled substance P. Ki values are calculated from IC50 values using the Cheng-Prusoff equation.
|
| Cell Assay |
Functional assays use cells expressing recombinant NK1 receptors. Receptor activation is measured by intracellular calcium mobilization using fluorescent dyes or by [35S]GTPγS binding. Orvepitant is pre-incubated with cells before substance P stimulation. IC50 values are determined from dose-response curves.
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| Animal Protocol |
Animal studies use rodent models of depression (forced swim test), anxiety (elevated plus maze), and pruritus (EGFRI-induced). Orvepitant is formulated in DMSO-PEG300-Tween 80-saline vehicle and administered orally at doses of 1-30 mg/kg. Behavioral assessments are conducted at defined time points post-administration. Plasma and brain concentrations are measured by LC-MS/MS.
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| References |
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| Additional Infomation |
Orvepitant is an organic molecular entity. Orvepitant has been used in clinical trials for the treatment of depression, major depressive disorder, post-traumatic stress disorder, and post-traumatic stress disorder (PTSD).
Drug Indications Treatment of refractory chronic cough |
| Molecular Formula |
C31H35F7N4O2
|
|---|---|
| Molecular Weight |
628.62402
|
| Exact Mass |
628.265
|
| CAS # |
579475-18-6
|
| PubChem CID |
9852175
|
| Appearance |
Typically exists as solid at room temperature
|
| LogP |
6.61
|
| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
10
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
44
|
| Complexity |
1020
|
| Defined Atom Stereocenter Count |
4
|
| SMILES |
FC1C=CC(=C(C)C=1)[C@H]1C[C@H](CCN1C(N(C)[C@H](C)C1C=C(C(F)(F)F)C=C(C(F)(F)F)C=1)=O)N1CCN2C(CC[C@H]2C1)=O
|
| InChi Key |
XWNBGDJPEXZSQM-VZOBGQTKSA-N
|
| InChi Code |
InChI=1S/C31H35F7N4O2/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/h4,6,12-15,19,24-25,27H,5,7-11,16-17H2,1-3H3/t19-,24+,25+,27-/m1/s1
|
| 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
|
| Synonyms |
GW823296; GW-823296; Orvepitant
|
| 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)
|
| 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
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|---|---|
| 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
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] 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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5908 mL | 7.9539 mL | 15.9079 mL | |
| 5 mM | 0.3182 mL | 1.5908 mL | 3.1816 mL | |
| 10 mM | 0.1591 mL | 0.7954 mL | 1.5908 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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