RolapitantOrally active neurokinin NK1 receptor antagonist. CAS# 552292-08-7 |
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Quality Control & MSDS
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| Cas No. | 552292-08-7 | SDF | Download SDF |
| PubChem ID | 10311306 | Appearance | Powder |
| Formula | C25H26F6N2O2 | M.Wt | 500.48 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Synonyms | SCH619734 | ||
| Solubility | DMSO : ≥ 30 mg/mL (59.94 mM) *"≥" means soluble, but saturation unknown. | ||
| Chemical Name | (5S,8S)-8-[[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]methyl]-8-phenyl-1,9-diazaspiro[4.5]decan-2-one | ||
| SMILES | CC(C1=CC(=CC(=C1)C(F)(F)F)C(F)(F)F)OCC2(CCC3(CCC(=O)N3)CN2)C4=CC=CC=C4 | ||
| Standard InChIKey | FIVSJYGQAIEMOC-ZGNKEGEESA-N | ||
| Standard InChI | InChI=1S/C25H26F6N2O2/c1-16(17-11-19(24(26,27)28)13-20(12-17)25(29,30)31)35-15-23(18-5-3-2-4-6-18)10-9-22(14-32-23)8-7-21(34)33-22/h2-6,11-13,16,32H,7-10,14-15H2,1H3,(H,33,34)/t16-,22-,23-/m1/s1 | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| Description | Rolapitant (SCH619734) is a potent, selective and orally active neurokinin NK1 receptor antagonist with a Ki of 0.66 nM.In Vitro:Rolapitant has a high affinity for the human NK1 receptor with a Ki of 0.66 nM and high selectivity over the human NK2 and NK3 subtypes of more than 1000-fold, as well as preferential affinity for human, guinea pig, gerbil and monkey NK1 receptors over rat, mouse and rabbit[1].In Vivo:Rolapitant reverses NK1 agonist-induced foot tapping in gerbils following both intravenous and oral administration up to 24 hours at a minimal effective dose (MED) of 0.1 mg/kg. Rolapitant is active at 0.1 and 1 mg/kg in both acute and delayed emesis models in ferrets, respectively, consistent with clinical data for other NK1 antagonists. Clinical efficacy of anti-emetics is highly correlated with efficacy in the ferret emesis model, suggesting rolapitant is a viable clinical candidate for this indication[1]. References: | |||||
Rolapitant Dilution Calculator
Rolapitant Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 1.9981 mL | 9.9904 mL | 19.9808 mL | 39.9616 mL | 49.952 mL |
| 5 mM | 0.3996 mL | 1.9981 mL | 3.9962 mL | 7.9923 mL | 9.9904 mL |
| 10 mM | 0.1998 mL | 0.999 mL | 1.9981 mL | 3.9962 mL | 4.9952 mL |
| 50 mM | 0.04 mL | 0.1998 mL | 0.3996 mL | 0.7992 mL | 0.999 mL |
| 100 mM | 0.02 mL | 0.0999 mL | 0.1998 mL | 0.3996 mL | 0.4995 mL |
| * Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. | |||||
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Description:
Kb: 0.17 nM
Neurokinin NK1 receptors have been shown to play a role in a variety of behavioral responses in both animals and humans that has lead to the development of selective antagonists for this receptor. Principal of NK1 antagonists is their inhibitory effects against emesis induced by a variety of emetogenic stimuli. Rolapitant (SCH 619734) is a potent, selective and orally active neurokinin NK1 receptor antagonist.
In vitro: In vitro studies indicate that rolapitant has a high affinity for the human NK1 receptor of 0.66 nM and high selectivity over the human NK2 and NK3 of >1000-fold, as well as preferential affinity for human, guinea pig, gerbil and monkey NK1 receptors over mouse, rat and rabbit. Rolapitant is a functionally competitive antagonist with a calculated Kb of 0.17 nM. [1].
In vivo: Rolapitant reversed NK1 agonist-induced foot tapping in gerbils following both intravenous and oral administration up to 24 hours at a minimal effective dose of 0.1 mg/kg. Rolapitant was efficacious at 0.1 and 1 mg/kg in both acute and delayed emesis models in ferrets, respectively, which is consistent with clinical data for other NK1 antagonists [1].
Clinical trial: Rolapitant is superior to placebo in reducing emetic episodes after surgery and reduces the incidence of vomiting in a dose-dependent manner. No differences were observed in side effect profile between rolapitant and placebo [2].
Reference:
[1] Duffy RA, Morgan C, Naylor R, Higgins GA, Varty GB, Lachowicz JE, Parker EM. Rolapitant (SCH 619734): a potent, selective and orally active neurokinin NK1 receptor antagonist with centrally-mediated antiemetic effects in ferrets. Pharmacol Biochem Behav. 2012 Jul;102(1):95-100.
[2] Gan TJ, Gu J, Singla N, Chung F, Pearman MH, Bergese SD, Habib AS, Candiotti KA, Mo Y, Huyck S, Creed MR, Cantillon M; Rolapitant Investigation Group. Rolapitant for the prevention of postoperative nausea and vomiting: a prospective, double-blinded, placebo-controlled randomized trial. Anesth Analg. 2011 Apr;112(4):804-12.
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Compatibility and Stability of Rolapitant Injectable Emulsion Admixed with Dexamethasone Sodium Phosphate.[Pubmed:28346199]
Int J Pharm Compd. 2017 Jan-Feb;21(1):66-75.
Neurokinin-1 receptor antagonist, 5-hydroxytryptamine-3 receptor antagonist, and dexamethasone combination therapy is the standard of care for the prevention of chemotherapy-induced nausea and vomiting. Herein, we describe the physical and chemical stability of an injectable emulsion of the Neurokinin-1 receptor antagonist Rolapitant 185 mg in 92.5 mL (free base, 166.5 mg in 92.5 mL) admixed with either 2.5 mL of dexamethasone sodium phosphate (10 mg) or 5 mL of dexamethasone sodium phosphate (20 mg). Admixtures were prepared and stored in two types of container closures (glass and Crystal Zenith plastic bottles) and four types of intravenous administration tubing sets (or intravenous tubing sets). The assessment of the physical and chemical stability was conducted on admixtures packaged in bottled samples stored at room temperature (20 degrees C to 25 degrees C under fluorescent light) and evaluated at 0, 1, and 6 hours. For admixtures in intravenous tubing sets, the assessment of physicochemical stability was performed after 0 and 7 hours of storage at 20 degrees C to 25 degrees C, and then after 20 hours (total 27 hours) under refrigeration (2 degrees C to 8 degrees C) and protected from light. Physical stability was assessed by visually examining the bottle contents under normal room light and measuring turbidity and particulate matter. Chemical stability was assessed by measuring the pH of the admixture and determining drug concentrations through high-performance liquid chromatographic analysis. Results showed that all samples were physically compatible throughout the duration of the study. The admixtures stayed within narrow and acceptable ranges in pH, turbidity, and particulate matter. Admixtures of Rolapitant and dexamethasone were chemically stable when stored in glass and Crystal Zenith bottles for at least 6 hours at room temperature, as well as in the four selected intravenous tubing sets for 7 hours at 20 degrees C to 25 degrees C and then for 20 (total 27 hours) hours at 2 degrees C to 8 degrees C. No loss of potency of any admixed component occurred in the samples stored at the temperature ranges studied.
Rolapitant (Varubi): A Substance P/Neurokinin-1 Receptor Antagonist for the Prevention of Chemotherapy-Induced Nausea and Vomiting.[Pubmed:28250699]
P T. 2017 Mar;42(3):168-172.
Rolapitant (Varubi) for the prevention of chemotherapy-induced nausea and vomiting.
Differential pharmacology and clinical utility of rolapitant in chemotherapy-induced nausea and vomiting.[Pubmed:28260945]
Cancer Manag Res. 2017 Feb 22;9:41-50.
Chemotherapy-induced nausea and vomiting (CINV) is a debilitating side effect of many cytotoxic chemotherapy regimens. CINV typically manifests during two well-defined time periods (acute and delayed phases). The acute phase is the first 24 hours after chemotherapy and is largely managed with 5-hydroxytryptamine 3 receptor antagonists. The delayed phase, a 5-day at-risk period during which patients are not often in direct contact with their health care provider, remains a significant unmet medical need. Neurokinin-1 (NK-1) receptor antagonists have demonstrated protection against acute and delayed CINV in patients treated with highly emetogenic chemotherapy and moderately emetogenic chemotherapy when used in combination with a 5-hydroxytryptamine 3 receptor antagonist and dexamethasone. Furthermore, recent data indicate that this protection is maintained over multiple treatment cycles. Rolapitant, a selective and long-acting NK-1 receptor antagonist, is approved as oral formulation for the prevention of delayed CINV in adults. This review discusses the differential pharmacology and clinical utility of Rolapitant in preventing CINV compared with other NK-1 receptor antagonists.
Integrated safety analysis of rolapitant with coadministered drugs from phase II/III trials: an assessment of CYP2D6 or BCRP inhibition by rolapitant.[Pubmed:28327932]
Ann Oncol. 2017 Jun 1;28(6):1268-1273.
Background: Rolapitant, a long-acting neurokinin (NK)1 receptor antagonist (RA), has demonstrated efficacy in prevention of chemotherapy-induced nausea and vomiting in patients administered moderately or highly emetogenic chemotherapy. Unlike other NK1 RAs, Rolapitant does not inhibit or induce cytochrome P450 (CYP) 3A4, but it does inhibit CYP2D6 and breast cancer resistance protein (BCRP). To analyze potential drug-drug interactions between Rolapitant and concomitant medications, this integrated safety analysis of four double-blind, randomized phase II or III studies of Rolapitant examined adverse events (AEs) by use versus non-use of drug substrates of CYP2D6 or BCRP. Patients and methods: Patients were randomized to receive either 180 mg oral Rolapitant or placebo approximately 1-2 h before chemotherapy in combination with a 5-hydroxytryptamine type 3 RA and dexamethasone. Data for treatment-emergent AEs (TEAEs) and treatment-emergent serious AEs (TESAEs) during cycle 1 were pooled across the four studies and summarized in the overall population and by concomitant use/non-use of CYP2D6 or BCRP substrate drugs. Results: In the integrated safety population, 828 of 1294 patients (64%) in the Rolapitant group and 840 of 1301 patients (65%) in the control group experienced at least one TEAE. Frequencies of common TEAEs were similar in the Rolapitant and control populations. Overall, 53% of patients received CYP2D6 substrate drugs, none of which had a narrow therapeutic index (like thioridazine or pimozide), and 63% received BCRP substrate drugs. When grouped by concomitant use versus non-use of CYP2D6 or BCRP substrate drugs, TEAEs and TESAEs occurred with similar frequency in the Rolapitant and control populations. Conclusions: The results of this study support the safety of Rolapitant as part of an antiemetic triple-drug regimen in patients receiving emetogenic chemotherapy, including those administered concomitant medications that are substrates of CYP2D6 or BCRP, such as ondansetron, docetaxel, or irinotecan.
