| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
NK1; Fosrolapitant targets the neurokinin-1 (NK1) receptor as a selective antagonist . It is a prodrug that is completely converted in vivo to its active metabolite, rolapitant . Rolapitant is a highly selective NK1 receptor antagonist with a prolonged elimination half-life of approximately 180 hours .
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|---|---|
| ln Vitro |
Fosrolapitant itself acts as an NK1 receptor antagonist . As a prodrug, it is designed to be converted in vivo to its active metabolite, rolapitant, rather than exerting direct pharmacological effects in vitro . Studies on the related compound rolapitant indicate that it does not inhibit CYP2C9, CYP2C19, CYP2D6, CYP3A4, or P-glycoprotein in vitro, suggesting a favorable drug-drug interaction profile for its active metabolite .
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| ln Vivo |
In a Phase I clinical trial (NCT05465681) involving 22 patients with solid tumors receiving highly emetogenic cisplatin-based chemotherapy, a single intravenous infusion of HR20013 (mixed formulation containing 218 mg fosrolapitant and 0.25 mg palonosetron) combined with oral dexamethasone achieved a complete response rate (no emesis and no rescue medication) of 90.9% during the overall phase (0-120 hours) and 86.4% during the beyond-delayed phase (120-168 hours) . Fosrolapitant was rapidly and completely converted to its active metabolite rolapitant in vivo, with a mean elimination half-life of 188.2 hours for rolapitant . The active metabolite M19 reached maximum plasma concentration at approximately 166.2 hours .
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| Enzyme Assay |
The available literature does not contain detailed step-by-step protocols for traditional enzyme or receptor binding assays (such as SPR, ITC, or radioligand binding) specifically for fosrolapitant. However, the following methodological information is available: NK1 receptor antagonism characterization – Fosrolapitant is described as an antagonist of the neurokinin-1 (NK1) receptor, with its active metabolite rolapitant being a highly selective NK1 receptor antagonist . The characterization likely involves competitive binding assays using radiolabeled substance P or other NK1 ligands, although specific protocols are not provided in the reviewed literature. CYP enzyme inhibition assessment – For the related compound rolapitant (the active metabolite), in vitro assays were conducted to assess inhibition of major cytochrome P450 enzymes (CYP2C9, CYP2C19, CYP2D6, CYP3A4) and P-glycoprotein, demonstrating minimal inhibitory effects .
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| Animal Protocol |
The available literature does not contain descriptions of animal experimental protocols for pharmacokinetic or efficacy studies of fosrolapitant. The primary source data for this compound comes from human clinical trials . The first approval of fosrolapitant/palonosetron was based on human studies, and no animal study protocols are provided in the reviewed publications.
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| ADME/Pharmacokinetics |
The following pharmacokinetic parameters were observed in a Phase I trial (n=19-22 patients) following a single 1-hour intravenous infusion of HR20013 containing 218 mg fosrolapitant and 0.25 mg palonosetron : Fosrolapitant (prodrug) – reached maximum plasma concentration (Cmax) immediately at the end of infusion (median Tmax = 1.0 h) with a Cmax of 9646.8 ng/mL, followed by a short terminal phase (mean t1/2 = 0.4 h); it was completely hydrolyzed into rolapitant . Rolapitant (active metabolite) – reached Cmax at approximately 1.2 hours (1304.4 ng/mL) with a mean elimination half-life of 188.2 hours; clearance (CL) was 1.1 L/h, apparent volume of distribution (V) was 300.0 L . M19 (major active metabolite of rolapitant) – reached Cmax at approximately 166.2 hours (150.9 ng/mL) . Palonosetron (co-formulated) – reached Cmax immediately at end of infusion (Tmax = 1.0 h) with a Cmax of 0.9 ng/mL and mean t1/2 of 51.5 hours . Dexamethasone (co-administered orally at 12 mg on Day 1) – reached Cmax at approximately 1.5 hours (106.0 ng/mL) .
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| Toxicity/Toxicokinetics |
In a Phase I clinical trial (n=22 patients), treatment-related adverse events occurred in 54.5% of patients receiving HR20013 (fosrolapitant/palonosetron) plus dexamethasone . The most common adverse events were: constipation (22.7%), increased blood pressure (18.2%), abdominal distension (13.6%), injection site reaction (9.1%), and increased neutrophil count (9.1%) . No grade ≥3 adverse events or serious adverse events were reported . All adverse events were manageable, and the safety profile was considered favorable . The literature notes that the active metabolite rolapitant has a low risk of drug-drug interactions due to minimal CYP enzyme inhibition .
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| References | |
| Additional Infomation |
Fosrolapitant (CAS: 2573694-38-7) has a molecular formula of C27H29F6N2O8P and a molecular weight of 654.49 . It is a phosphate ester prodrug of rolapitant, designed for intravenous administration . The compound is being developed by Fujian Shengdi Pharmaceutical Co., Ltd. . The fixed-dose combination HR20013 contains 218 mg fosrolapitant (equimolar to 166.5 mg intravenous rolapitant emulsion) and 0.25 mg palonosetron . This combination received its first approval in China on May 29, 2025, for the prevention of acute and delayed nausea and vomiting caused by highly emetogenic chemotherapy in adults . The combination is also being investigated for postoperative nausea and vomiting . Unlike fosaprepitant (the IV prodrug of aprepitant), which is a weak CYP3A4 inhibitor and requires dexamethasone dose reduction, rolapitant (the active form of fosrolapitant) does not significantly inhibit major CYP enzymes, suggesting a lower potential for drug-drug interactions . This property may offer clinical advantages when co-administered with other medications metabolized by cytochrome P450 enzymes.
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| Molecular Formula |
C27H29F6N2O8P
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|---|---|
| Molecular Weight |
654.49
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| Exact Mass |
654.1565718
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| Elemental Analysis |
C, 49.55; H, 4.47; F, 17.42; N, 4.28; O, 19.56; P, 4.73
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| CAS # |
2573694-38-7
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| PubChem CID |
163871173
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| Appearance |
Typically exists as solids at room temperature
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| LogP |
3.1
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
14
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
44
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| Complexity |
1060
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| Defined Atom Stereocenter Count |
3
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| SMILES |
C[C@H](C1=CC(=CC(=C1)C(F)(F)F)C(F)(F)F)OC[C@]2(CC[C@]3(CCC(=O)N3)CN2C(=O)OCOP(=O)(O)O)C4=CC=CC=C4
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| InChi Key |
PKXQGSOAMISYFP-LJXNEXSDSA-N
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| InChi Code |
InChI=1S/C27H29F6N2O8P/c1-17(18-11-20(26(28,29)30)13-21(12-18)27(31,32)33)41-15-25(19-5-3-2-4-6-19)10-9-24(8-7-22(36)34-24)14-35(25)23(37)42-16-43-44(38,39)40/h2-6,11-13,17H,7-10,14-16H2,1H3,(H,34,36)(H2,38,39,40)/t17-,24-,25-/m1/s1
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| Chemical Name |
phosphonooxymethyl (5S,8S)-8-[[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]methyl]-2-oxo-8-phenyl-1,9-diazaspiro[4.5]decane-9-carboxylate
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| Synonyms |
Fosrolapitant; 2573694-38-7; 1,7-Diazaspiro[4.5]decane-7-carboxylic acid, 8-[[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]methyl]-2-oxo-8-phenyl-, (phosphonooxy)methyl ester, (5S,8S)-; fosrolapitant [INN]; M5QGY92X8B;
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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 | 1.5279 mL | 7.6395 mL | 15.2791 mL | |
| 5 mM | 0.3056 mL | 1.5279 mL | 3.0558 mL | |
| 10 mM | 0.1528 mL | 0.7640 mL | 1.5279 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.
Link: https://clinicaltrials.gov/ct2/show/NCT06554184
Conditions:Nausea and Vomiting Associated With Moderate Emetic Risk Anticancer AgentsProducts are for research use only; We do not sell to patients
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