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| 10mg |
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| Targets |
The primary target of rolapitant is the neurokinin-1 receptor (NK1 receptor), a member of the G protein-coupled receptor family. It competitively binds to and blocks the activity of the NK1 receptor in the central nervous system, thereby inhibiting the interaction with the endogenous ligand substance P. Rolapitant exhibits high affinity for the human NK1 receptor with a Ki value of 0.66 nM and demonstrates >1000-fold selectivity over the human NK2 and NK3 subtypes. Compared to other NK1 receptor antagonists like aprepitant, rolapitant has both a more rapid onset of action and a much longer half-life.
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| ln Vitro |
Rolapitant exhibits superior affinity for NK1 receptors in humans, guinea pigs, gerbils, and monkeys compared to rat, mouse, and rabbit, and it has over 1000-fold selectivity for human NK2 and NK3 isoforms [1]. In CHO cells expressing human NK1 receptor, rolapitant (1-1000 nM) competitively and concentration-dependently blocks calcium efflux generated by GR-73632, an NK1 receptor agonist [1].
Rolapitant demonstrates high selectivity and potent NK1 receptor antagonistic activity in vitro. In cell-free radioligand binding assays, rolapitant exhibits high affinity for the human NK1 receptor with a Ki value of 0.66 nM and displays >1000-fold selectivity over the human NK2 and NK3 subtypes. In CHO cells expressing the human NK1 receptor, rolapitant (1-1000 nM) inhibits GR-73632 (an NK1 receptor agonist)-induced calcium efflux in a concentration-dependent and competitive manner, with a calculated Kb value of 0.17 nM. Furthermore, rolapitant exhibits species selectivity for the NK1 receptor, showing preferential affinity for human, guinea pig, gerbil, and monkey NK1 receptors over rat, mouse, and rabbit. |
| ln Vivo |
In Mongolian gerbils, rolapitant (0.03–1 mg/kg orally, 0.3–1 mg/kg intravenously; single dose) reduces the foot tapping response induced by GR-73632 [1]. Rolapitant (0.03-1 mg/kg; oral; single dose; observed for 72 hours) inhibits the acute vomiting that ferrets experience when given apomorphine and cisplatin [1].
Rolapitant demonstrates centrally-mediated antiemetic activity in various animal models. In gerbils, a single oral or intravenous administration of rolapitant (minimal effective dose of 0.1 mg/kg) reverses NK1 agonist-induced foot-tapping response for up to 24 hours. In ferrets, rolapitant (0.03-1 mg/kg, oral) effectively blocks apomorphine- and cisplatin-induced acute emesis and shows activity in both acute and delayed emesis models at 0.1 and 1 mg/kg, respectively. Clinical efficacy of antiemetics is highly correlated with efficacy in the ferret emesis model, suggesting rolapitant's clinical effectiveness. |
| Enzyme Assay |
Membrane Preparation: Harvest CHO cells expressing human NK1 receptors, lyse cells, and extract membrane fractions via centrifugation.
Radioligand Binding Assay: Incubate membranes with radioligand (e.g., [³H]substance P or [³H]GR-73632) and various concentrations of rolapitant in assay buffer at room temperature.
Define Non-specific Binding: Use a high concentration of unlabeled ligand or NK1 receptor antagonist to define non-specific binding.
Harvest & Count: Terminate the reaction by rapid vacuum filtration through GF/B filters. Wash filters, dry them, and measure bound radioactivity using a liquid scintillation counter.
Data Analysis: Plot competitive binding curves and calculate the Ki value for rolapitant (0.66 nM).
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| Cell Assay |
Cell Culture: Seed CHO cells stably expressing human NK1 receptors into appropriate culture plates and culture to suitable confluence.
Calcium Flux Assay: Load cells with a calcium-sensitive dye (e.g., Fluo-4 AM) and pre-incubate with varying concentrations of rolapitant.
Agonist Stimulation: Add NK1 receptor agonist GR-73632 to stimulate, and detect changes in intracellular calcium concentration using a fluorescence plate reader or HTS system.
Data Analysis: Rolapitant inhibits agonist-induced calcium efflux in a concentration-dependent and competitive manner, with a calculated Kb value of 0.17 nM.
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| Animal Protocol |
Animal/Disease Models: Female Mongolian gerbil (30-60 g; anesthetized with oxygen:isoflurane mixture immediately after 4 h PO or immediately after IV, followed by ICV injection of 5 μl of 3 pmol GR-73632 solution) [1]
Doses: 0.03 orally , 0.1, 0.3 and 1 mg/kg, IV 0.3 and 1 mg/kg Dosing: Oral or IV, single dose Experimental Results: GR-73632-induced foot tapping response was attenuated when administered PO 4, dose-dependent One hour before the dependence test, the ID90 is 0.3 mg/kg, and foot pedaling is inhibited for at least 24 hrs (hrs (hours)). When administered intravenously (iv) (iv)(iv), GR-73632 induced a dose-dependent blockade of foot tapping, with complete blockade observed at 1 mg/kg. Animal/Disease Models: Ferrets (treated with 0.125 mg/kg apomorphine subcutaneously (sc) (sc) or 10 mg/kg cisplatin intraperitoneally (ip) (ip)) [1] Doses: 0.03, 0.1, 0.3 and 1 mg/kg Route of Administration: PO; single dose; Results observed for 72 hrs (hrs (hours)): Blocked dose-dependent acute vomiting in ferrets induced by apomorphine and cisplatin. Retching and vomiting were significan |
| References |
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| Additional Infomation |
Rolapitant hydrochloride (anhydrous form) is the hydrochloride salt of irinotecan reacted with an equimolar amount of hydrochloric acid. It (in hydrated form) is used to prevent delayed nausea and vomiting induced by initial and repeated courses of emetogenic chemotherapy for cancer. It has antiemetic and neurokinin-1 receptor antagonistic effects. It contains rorapitan (1+).
See also: Rolapitant hydrochloride (note moved to). |
| Molecular Formula |
C25H27CLF6N2O2
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| Molecular Weight |
536.937506914139
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| Exact Mass |
536.167
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| Elemental Analysis |
C, 55.92; H, 5.07; Cl, 6.60; F, 21.23; N, 5.22; O, 5.96
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| CAS # |
858102-79-1
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| Related CAS # |
Rolapitant;552292-08-7;Rolapitant hydrochloride hydrate;914462-92-3
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| PubChem CID |
71587824
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
7.189
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
36
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| Complexity |
731
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| Defined Atom Stereocenter Count |
3
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| SMILES |
Cl.FC(C1C=C(C(F)(F)F)C=C(C=1)[C@@H](C)OC[C@@]1(C2C=CC=CC=2)CC[C@]2(CCC(N2)=O)CN1)(F)F
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| InChi Key |
VEWAWEMXVUFANV-PVBCUUEWSA-N
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| InChi Code |
InChI=1S/C25H26F6N2O2.ClH/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);1H/t16-,22-,23-;/m1./s1
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| Chemical Name |
(5S,8S)-8-[[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]methyl]-8-phenyl-1,9-diazaspiro[4.5]decan-2-one;hydrochloride
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| Synonyms |
858102-79-1; Rolapitant (hydrochloride); (5S,8S)-8-[[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]methyl]-8-phenyl-1,9-diazaspiro[4.5]decan-2-one;hydrochloride; C25H27ClF6N2O2; 1,7-Diazaspiro[4.5]decan-2-one, 8-[[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]methyl]-8-phenyl-, hydrochloride (1:1), (5S,8S)-; 1,7-Diazaspiro[4.5]decan-2-one, 8-[[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]methyl]-8-phenyl-, monohydrochloride, (5S,8S)- (9CI); Rolapitant hydrochloride; Sch 619734;
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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 | 1.8624 mL | 9.3120 mL | 18.6241 mL | |
| 5 mM | 0.3725 mL | 1.8624 mL | 3.7248 mL | |
| 10 mM | 0.1862 mL | 0.9312 mL | 1.8624 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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