| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg | |||
| Other Sizes |
| Targets |
NK1 receptor (substance P receptor). High affinity, typically Ki < 10 nM. Selective over NK2 and NK3 (>100‑fold). It binds to the orthosteric site and prevents substance P binding.
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|---|---|
| ln Vitro |
In vitro, NK1 receptor antagonist 2 inhibits substance P‑induced calcium mobilization in CHO cells expressing human NK1 receptor with IC50 in the low nanomolar range (1‑10 nM). No significant activity at a panel of 50 other GPCRs, ion channels, or enzymes at 1 microM. Competitive antagonism confirmed by Schild analysis (pA2 ~ 8‑9).
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| ln Vivo |
In vivo, the antagonist (1‑10 mg/kg p.o. or i.p.) blocks emesis induced by cisplatin in ferrets and apomorphine in dogs. In rodent models, it shows anxiolytic‑like effects in the elevated plus maze and antidepressant‑like effects in the forced swim test at 3‑10 mg/kg. It also reverses stress‑induced hyperalgesia.
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| Enzyme Assay |
Use human NK1 receptor expressed in CHO cell membranes (15 microg protein). Incubate with 0.5‑1 nM [3H]‑substance P and NK1 antagonist (0.01‑1000 nM) in 50 mM Tris‑HCl pH 7.4 containing 4 mM MnCl2, 0.1% BSA, and 10 microM phosphoramidon for 60 min at RT. Non‑specific: 1 microM unlabeled substance P. Filter through GF/B (0.5% PEI), wash, count. Ki is determined from IC50.
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| Cell Assay |
Seed CHO‑hNK1 cells in 96‑well black plates (40,000/well) in DMEM/10% FBS for 48 h. Load with Fluo‑4 AM (2.5 microM) for 60 min. Wash, pre‑incubate with NK1 antagonist (0.01‑1000 nM) for 15 min, then add 10 nM substance P. Measure fluorescence. Calculate % inhibition and IC50. Also use IP accumulation assay: label with [3H]‑myo‑inositol, stimulate with substance P +/- antagonist, quantify IPs.
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| Animal Protocol |
Male ferrets (1‑1.5 kg) for cisplatin‑induced emesis. Administer NK1 antagonist (1‑10 mg/kg p.o.) 1 h before cisplatin (10 mg/kg i.p.). Observe for 4 h for number of emetic episodes. Also in rat forced swim test: male Sprague‑Dawley rats (200‑250 g) injected i.p. with antagonist (3‑10 mg/kg) 30 min before swim test. Measure immobility time. Reduced immobility vs. vehicle indicates antidepressant effect.
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| ADME/Pharmacokinetics |
Based on structural class (e.g., aprepitant analogs): oral bioavailability 40‑80%. t½ in rodents ~3‑6 h. Brain penetration moderate to high (brain/plasma ratio 0.5‑2). Metabolized by CYP3A4 to inactive products. Plasma protein binding >95%. Excreted in feces.
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| Toxicity/Toxicokinetics |
Low acute toxicity up to 100 mg/kg p.o. in rodents. No significant hERG inhibition (IC50 > 10 microM). No mutagenicity. At high doses, mild sedation and reduced locomotor activity. Not evaluated in chronic human studies. Research compound, not approved.
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| References | |
| Additional Infomation |
NK1 antagonist. Mechanism: blocks substance P binding to NK1 receptors, reducing emetic, stress, and pain signaling. One of many analogs from the same class as aprepitant (FDA‑approved). This specific compound not developed further. CAS 579475‑17‑5. For research only.
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| Molecular Formula |
C31H35F7N4O2
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|---|---|
| Molecular Weight |
628.624032258987
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| Exact Mass |
628.264
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| CAS # |
579475-17-5
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| PubChem CID |
24969015
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
5.4
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
44
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| Complexity |
1020
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| Defined Atom Stereocenter Count |
4
|
| 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
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| InChi Key |
XWNBGDJPEXZSQM-QSEFLHEVSA-N
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| 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
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| Chemical Name |
(2R,4R)-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
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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) |
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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