Synonym
MK0517; MK 0517; MK-0517; Fosaprepitant; Fosaprepitant dimeglumine; Emend; Inemend.
IUPAC/Chemical Name
(2R,3R,4R,5S)-6-(methylamino)hexane-1,2,3,4,5-pentaol hemi((3-(((2R,3S)-2-((R)-1-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(4-fluorophenyl)morpholino)methyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)phosphonate)
InChi Key
VRQHBYGYXDWZDL-OOZCZQCLSA-N
InChi Code
InChI=1S/C23H22F7N4O6P.2C7H17NO5/c1-12(14-8-15(22(25,26)27)10-16(9-14)23(28,29)30)40-20-19(13-2-4-17(24)5-3-13)33(6-7-39-20)11-18-31-21(35)34(32-18)41(36,37)38;2*1-8-2-4(10)6(12)7(13)5(11)3-9/h2-5,8-10,12,19-20H,6-7,11H2,1H3,(H,31,32,35)(H2,36,37,38);2*4-13H,2-3H2,1H3/t12-,19+,20-;2*4-,5+,6+,7+/m100/s1
SMILES Code
O=C(N1)N(P(O)(O)=O)N=C1CN2CCO[C@H](O[C@H](C)C3=CC(C(F)(F)F)=CC(C(F)(F)F)=C3)[C@@H]2C4=CC=C(F)C=C4.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)CNC.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)CNC
Appearance
white solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO or water
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Related CAS#
CAS# 265121-04-8 (Fosaprepitant dimeglumine salt);
CAS#172673-20-0 (Fosaprepitant)
Biological target:
Fosaprepitant dimeglumine (MK-0517) is a prodrug of Aprepitant (HY-10052) and is a neurokinin-1 receptor antagonist.
In vitro activity:
Fosaprepitant is likely to be combined and stored in the same intravenous (IV) bag with 5-HT3 antagonists and corticosteroids, therefore the in vitro compatibility of fosaprepitant with these agents and other IV diluents was assessed. Fosaprepitant (1 mg/mL in 0.9 % sodium chloride injection solution) was combined in binary or tertiary fashion with therapeutic-dose preparations of a 5-HT3 antagonist (ondansetron, granisetron, palonosetron, or tropisetron) and/or a corticosteroid (dexamethasone sodium phosphate or methylprednisolone sodium succinate). For diluent compatibility assessment, fosaprepitant was also prepared 1 mg/mL in 0.9 % sodium chloride injection solution, water for injection, or 5 % dextrose injection solution. Fosaprepitant demonstrated compatibility when combined in the same IV infusion bag with common 5-HT3 antagonists and corticosteroids for storage and IV coadministration, with the exception of palonosetron (incompatible under all experimental conditions) and tropisetron (incompatible unless combined with a corticosteroid). No incompatibility was observed between fosaprepitant and any of the 3 diluents tested. Use of fosaprepitant in combination with other antiemetics may provide a flexible option for administration of antiemetics to patients receiving moderately or highly emetogenic chemotherapy.
Cancer Chemother Pharmacol. 2013 Sep;72(3):509-13. https://pubmed.ncbi.nlm.nih.gov/23860958/
In vivo activity:
The aim of this study was to test the efficacy of Neurokinin-1 Receptor (NK-1R) antagonist -Fosaprepitant- in inducing regression of established corneal neovascularization (CNV). Twenty C57BL/6 mice underwent alkali burn. Seven days later, when corneal neovessels had developed, they received Fosaprepitant 10 mg/ml, administered topically six times a day in the right eye for 10 days. In parallel, a group of 20 causticated mice was treated with normal saline, as control. A second independent experiment was also performed (n = 10/group). Finally, ten healthy mice received the same topical treatment for 10 days to evaluate Fosaprepitant safety. Topical Fosaprepitant administration induced a significant reduction of (i) CD31+ blood corneal neovessels (-27%, p = 0.0132), (ii) LYVE1+ lymphatic corneal neovessels (-31%, p = 0.0118) and (iii) CD45+ leucocyte infiltration (-36%; p = 0.0237). The second independent experiment confirmed these data. Moreover, Fosaprepitant-treated corneas showed a reduction in opacity, no impairment in corneal fluorescein staining and decreased infiltration of neutrophils (-72%, p < 0.05) and macrophages (-75%, p < 0.01). Finally, topical Fosaprepitant was not toxic to the ocular surface: no signs of conjunctivitis, opacity, perforations or corneal fluorescein staining were detected. Similarly, corneal TUJ1+ nerve density was not affected. The data suggests that NK-1R antagonists, such as Fosaprepitant, could be a new, promising therapeutic tool to inhibit CNV after this has been established.
Acta Ophthalmol. 2017 Nov;95(7):e641-e648. https://onlinelibrary.wiley.com/doi/full/10.1111/aos.13304
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
100.0 |
99.52 |
| H20 |
75.0 |
74.64 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
1,004.84
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Sun S, Schaller J, Placek J, Duersch B. Compatibility of intravenous fosaprepitant with intravenous 5-HT3 antagonists and corticosteroids. Cancer Chemother Pharmacol. 2013 Sep;72(3):509-13. doi: 10.1007/s00280-013-2201-2. Epub 2013 Jul 17. PMID: 23860958.
2. Bignami F, Lorusso A, Rama P, Ferrari G. Growth inhibition of formed corneal neovascularization following Fosaprepitant treatment. Acta Ophthalmol. 2017 Nov;95(7):e641-e648. doi: 10.1111/aos.13304. Epub 2017 Feb 15. PMID: 28205389
3. Prasoon P, Gupta S, Kumar R, Gautam M, Kaler S, Ray SB. Role of fosaprepitant, a neurokinin Type 1 receptor antagonist, in morphine-induced antinociception in rats. Indian J Pharmacol. 2016 Jul-Aug;48(4):394-398. doi: 10.4103/0253-7613.186198. PMID: 27756950; PMCID: PMC4980927.
In vitro protocol:
1. Sun S, Schaller J, Placek J, Duersch B. Compatibility of intravenous fosaprepitant with intravenous 5-HT3 antagonists and corticosteroids. Cancer Chemother Pharmacol. 2013 Sep;72(3):509-13. doi: 10.1007/s00280-013-2201-2. Epub 2013 Jul 17. PMID: 23860958.
In vivo protocol:
1. Bignami F, Lorusso A, Rama P, Ferrari G. Growth inhibition of formed corneal neovascularization following Fosaprepitant treatment. Acta Ophthalmol. 2017 Nov;95(7):e641-e648. doi: 10.1111/aos.13304. Epub 2017 Feb 15. PMID: 28205389. 2. Prasoon P, Gupta S, Kumar R, Gautam M, Kaler S, Ray SB. Role of fosaprepitant, a neurokinin Type 1 receptor antagonist, in morphine-induced antinociception in rats. Indian J Pharmacol. 2016 Jul-Aug;48(4):394-398. doi: 10.4103/0253-7613.186198. PMID: 27756950; PMCID: PMC4980927.
1: Grunberg S, Chua D, Maru A, Dinis J, DeVandry S, Boice JA, Hardwick JS, Beckford E, Taylor A, Carides A, Roila F, Herrstedt J. Single-dose fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with cisplatin therapy: randomized, double-blind study protocol--EASE. J Clin Oncol. 2011 Apr 10;29(11):1495-501. Epub 2011 Mar 7. PubMed PMID: 21383291.
2: Marbury TC, Ngo PL, Shadle CR, Jin B, Panebianco D, Caro L, Valentine J, Murphy G. Pharmacokinetics of Oral Dexamethasone and Midazolam When Administered With Single-Dose Intravenous 150 mg Fosaprepitant in Healthy Adult Subjects. J Clin Pharmacol. 2011 Jan 5. [Epub ahead of print] PubMed PMID: 21209230.
3: Langford P, Chrisp P. Fosaprepitant and aprepitant: an update of the evidence for their place in the prevention of chemotherapy-induced nausea and vomiting. Core Evid. 2010 Oct 21;5:77-90. PubMed PMID: 21042544; PubMed Central PMCID: PMC2963924.
4: Colon-Gonzalez F, Kraft WK. Pharmacokinetic evaluation of fosaprepitant dimeglumine. Expert Opin Drug Metab Toxicol. 2010 Oct;6(10):1277-86. Review. PubMed PMID: 20795794; PubMed Central PMCID: PMC3155701.
5: Marbury TC, Jin B, Panebianco D, Murphy MG, Sun H, Evans JK, Han TH, Constanzer ML, Dru J, Shadle CR. Lack of effect of aprepitant or its prodrug fosaprepitant on QTc intervals in healthy subjects. Anesth Analg. 2009 Aug;109(2):418-25. PubMed PMID: 19608812.
6: Van Belle SJ, Cocquyt V. Fosaprepitant dimeglumine (MK-0517 or L-785,298), an intravenous neurokinin-1 antagonist for the prevention of chemotherapy induced nausea and vomiting. Expert Opin Pharmacother. 2008 Dec;9(18):3261-70. Review. PubMed PMID: 19040346.
7: Navari RM. Fosaprepitant: a neurokinin-1 receptor antagonist for the prevention of chemotherapy-induced nausea and vomiting. Expert Rev Anticancer Ther. 2008 Nov;8(11):1733-42. Review. PubMed PMID: 18983233.
8: Olver IN. Prevention of chemotherapy-induced nausea and vomiting: focus on fosaprepitant. Ther Clin Risk Manag. 2008 Apr;4(2):501-6. PubMed PMID: 18728837; PubMed Central PMCID: PMC2504061.
9: Navari RM. Fosaprepitant (MK-0517): a neurokinin-1 receptor antagonist for the prevention of chemotherapy-induced nausea and vomiting. Expert Opin Investig Drugs. 2007 Dec;16(12):1977-85. Review. PubMed PMID: 18042005.
10: Lasseter KC, Gambale J, Jin B, Bergman A, Constanzer M, Dru J, Han TH, Majumdar A, Evans JK, Murphy MG. Tolerability of fosaprepitant and bioequivalency to aprepitant in healthy subjects. J Clin Pharmacol. 2007 Jul;47(7):834-40. Epub 2007 May 24. PubMed PMID: 17525168.
