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5mg |
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10mg |
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25mg |
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50mg |
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100mg |
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250mg |
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Purity: ≥98%
Netupitant (formerly CID-6451149; AGE-94200; Ro 67-3189) is an orally bioavailable neurokinin 1 (NK1) receptor antagonist with potential antiemetic activity. It inhibits NK1 with a Ki of 0.95 nM. In 2018, the FDA approved the combination medication netupitant/palonosetron to prevent nausea and vomiting caused by acute and delayed chemotherapy, including highly emetogenic chemotherapy like cisplatin. Netupitant inhibits NK1-receptor binding of the endogenous tachykinin neuropeptide substance P (SP) by competitively binding to and blocking the activity of human substance P/NK1 receptors in the central nervous system (CNS). This may prevent chemotherapy-induced nausea and vomiting (CINV).
Targets |
Neurokinin-1 receptor
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ln Vitro |
Netupitant (CID-6451149) exhibits a high affinity for the human NK1 receptor (pKi=9.0), exhibiting selectivity over NK2 and NK3 (pKi=5.8 for both sites) by more than 1000 times[2].
Netupitant (1, 10, 100 nM) concentration-dependently antagonizes substance P's stimulatory effects, exhibiting irreversible antagonism (pKB=8.87) in CHO NK1 cells[2]. |
ln Vivo |
Netupitant (CID-6451149; 1–10 mg/kg; ip) inhibits mice's typical scratching, biting, and licking response in a dose-dependent manner. When NK1 agonists are injected intracerebroventricularly, gerbils will tap their feet. Netupitant, administered intraperitoneally (ID50 1.5 mg/kg) or orally (ID50 0.5 mg/kg), will counteract this behavior in a dose-dependent manner[2].
Netupitant (0.1-3 mg/kg; intraperitoneally) inhibits the responses to SP-methylester (SP-OMe) in a concentration-dependent manner (mean pKB=9.24) in the detrusor muscle. Netupitant reduces the frequency of the bladder's reflex contractions[3]. |
Cell Assay |
Cells are pre-incubated in growth media (control) or media containing antagonists for one hour at 37°C. To guarantee receptor saturation, antagonist concentrations must be at least 30 times higher than the Kd value. In order to allow antagonists that are still attached to receptors to dissociate, antagonists are removed from the cells after preincubation and they are rinsed with growth media alone for an extra hour. Then, isosmotic HEPES buffer (pH 7.4, 20 mM) is added to the cell media. This buffer contains the following concentrations of SP and NaCl: 3 nM to 1 mM; KCl (2 mM), MgCl2 (1 mM), CaCl2 (2 mM), Fluo-4 acetoxymethyl (AM) ester (2 mM), pluronic acid (0.04%), and MgCl2 (1 mM). The last incubation took place at 37 °C for one hour. In order to sequester the AM ester molecules into micelles for cellular uptake, pluronic acid is added as a nonionic surfactant.
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References |
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Molecular Formula |
C30H32F6N4O
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Molecular Weight |
578.59
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Exact Mass |
578.25
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Elemental Analysis |
C, 62.28; H, 5.57; F, 19.70; N, 9.68; O, 2.77
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CAS # |
290297-26-6
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Related CAS # |
Netupitant-d6; 2070015-31-3; Netupitant metabolite N-desmethyl Netupitant; 290296-72-9; N-desmethyl Netupitant-d6; Netupitant metabolite Netupitant N-oxide; 910808-11-6; Netupitant N-oxide-d6; Netupitant metabolite Monohydroxy Netupitant; 910808-12-7; Monohydroxy Netupitant-d6
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Appearance |
White solid powder
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SMILES |
CC1=CC=CC=C1C2=CC(=NC=C2N(C)C(=O)C(C)(C)C3=CC(=CC(=C3)C(F)(F)F)C(F)(F)F)N4CCN(CC4)C
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InChi Key |
WAXQNWCZJDTGBU-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C30H32F6N4O/c1-19-8-6-7-9-23(19)24-17-26(40-12-10-38(4)11-13-40)37-18-25(24)39(5)27(41)28(2,3)20-14-21(29(31,32)33)16-22(15-20)30(34,35)36/h6-9,14-18H,10-13H2,1-5H3
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Chemical Name |
2-[3,5-bis(trifluoromethyl)phenyl]-N,2-dimethyl-N-[4-(2-methylphenyl)-6-(4-methylpiperazin-1-yl)pyridin-3-yl]propanamide
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Synonyms |
AGE-94200; Ro67-3189; AGE 94200; Ro 67-3189/000; AGE94200; Ro 67-3189; Ro-67-3189; Netupitant
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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: 2~9.1 mg/mL (3.5~15.71 mM)
Ethanol: ~100 mg/mL |
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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 | 1.7283 mL | 8.6417 mL | 17.2834 mL | |
5 mM | 0.3457 mL | 1.7283 mL | 3.4567 mL | |
10 mM | 0.1728 mL | 0.8642 mL | 1.7283 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.
NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
NCT04931108 | Recruiting | Drug: Dexamethasone Drug: Olanzapine Other: Placebo |
Breast Carcinoma | University of Rochester NCORP Research Base |
May 19, 2018 | Phase 3 |
NCT03563248 | Active Recruiting |
Drug: FOLFIRINOX Drug: Losartan |
Pancreatic Cancer | Massachusetts General Hospital | August 10, 2018 | Phase 2 |
NCT04817189 | Recruiting | Drug: NEPA (300mg netupitant/0.5mg palonosetron) Drug: Dexamethasone, 8 mg (oral) or equivalent IV dose |
Chemotherapy-induced Nausea and Vomiting |
Helsinn Healthcare SA | February 1, 2021 | Phase 4 |
NCT06102447 | Not yet recruiting | Drug: Netopitam Palonosetron capsules and dexamethasone |
Head and Neck Squamous Cell Carcinoma (HNSCC) |
Sichuan Cancer Hospital and Research Institute |
November 1, 2023 | Not Applicable |
NCT03204279 | Completed | Drug: Netupitant Drug: Palonosetron |
Chemotherapy-induced Nausea and Vomiting (CINV) |
Helsinn Healthcare SA | August 31, 2017 | Phase 2 |
First and second concentration-response curves (CRCs) to SP-OMe in guinea-pig isolated urinary bladders incubated with netupitant at (A) 1 nM; (B) 3 nM; (C) 10 nM; (D) 30 nM. Front Pharmacol . 2016 Aug 4:7:234. td> |
Cystometric recordings in the isovolumetric model obtained following administration of vehicle, netupitant at 0.3 and 3 mg/Kg, i.v. and L-733,060 at 3 mg/kg, i.v. Front Pharmacol . 2016 Aug 4:7:234. td> |
Effect of netupitant or L-733,060 on BCA (n = 10 for each). Front Pharmacol . 2016 Aug 4:7:234. td> |