Fosaprepitant dimeglumine (also known as L-758298 dimeglumine; MK0517 dimeglumine) is a neurokinin-1 receptor antagonist for the prevention of chemotherapy-induced nausea and vomiting. Fosaprepitant is injected intravenously as an antiemetic medication. Merck & Co. created fosaprepitant, which was authorized as an Aprepitant prodrug. It helps to prevent both acute and delayed nausea and vomiting brought on by chemotherapy. Aprepitant, the active moiety, is a substrate, inducer, and inhibitor of CYP3A4, while fosaprepitant is a weak inhibitor of CYP3A4.

Physicochemical Properties

Molecular Formula	C37H56F7N6O16P
Molecular Weight	1004.8337
Exact Mass	1004.34
Elemental Analysis	C, 44.23; H, 5.62; F, 13.23; N, 8.36; O, 25.48; P, 3.08
CAS #	265121-04-8
Related CAS #	Fosaprepitant; 172673-20-0; Fosaprepitant-d4 dimeglumine
PubChem CID	136086851
Appearance	White solid powder
Hydrogen Bond Donor Count	9
Hydrogen Bond Acceptor Count	21
Rotatable Bond Count	13
Heavy Atom Count	54
Complexity	1130
Defined Atom Stereocenter Count	7
SMILES	P(N1C(N([H])C(C([H])([H])N2C([H])([H])C([H])([H])O[C@@]([H])([C@]2([H])C2C([H])=C([H])C(=C([H])C=2[H])F)O[C@]([H])(C([H])([H])[H])C2C([H])=C(C(F)(F)F)C([H])=C(C(F)(F)F)C=2[H])=N1)=O)(=O)(O[H])O[H].O([H])[C@]([H])([C@]([H])(C([H])([H])N([H])C([H])([H])[H])O[H])[C@@]([H])([C@@]([H])(C([H])([H])O[H])O[H])O[H].O([H])[C@]([H])([C@]([H])(C([H])([H])N([H])C([H])([H])[H])O[H])[C@@]([H])([C@@]([H])(C([H])([H])O[H])O[H])O[H]
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
Chemical Name	[3-[[(2R,3S)-2-[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-(4-fluorophenyl)morpholin-4-yl]methyl]-5-oxo-4H-1,2,4-triazol-1-yl]phosphonic acid;(2R,3R,4R,5S)-6-(methylamino)hexane-1,2,3,4,5-pentol
Synonyms	MK0517; MK 0517; MK-0517; Fosaprepitant dimeglumine; Fosaprepitant dimeglumine salt; Ivemend; Fosaprepitant meglumine; MK-0517; Fosaprepitant (dimeglumine); UNII-D35FM8T64X; Emend; Inemend
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: (1). This product is not stable in solution, please use freshly prepared working solution for optimal results.(2). Please store this product in a sealed and protected environment, avoid exposure to moisture.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	Neurokinin-1 receptor
ln Vitro	Fosaprepitant (MK-0517, L-758,298) is a phosphoryl prodrug for aprepitant. A corticosteroid and a 5-HT 3 receptor antagonist are approved as combination therapies with the selective substance P (NK-1 receptor) antagonist aprepitant to prevent acute and delayed chemotherapy-induced nausea and vomiting. [1]
ln Vivo	Fosaprepitant is intravenously administered and within 30 minutes, transforms into an aprepitant due to the action of ubiquitous phosphatases. Fosaprepitant has a well-tolerated maximum dosage of 150 mg (1 mg/ml), and its AUC for Fosaprepitant 115 mg and Aprecipitant 125 mg are bioequivalent. On day 1 of a 3-day oral aprepitant regimen, fosaprepitant 115 mg has been submitted for FDA approval as an alternative. On days 2 and 3, oral aprepitant is administered. [1]
Animal Protocol	Sprague-Dawley rats were injected with morphine (10 mg/kg twice daily) and/or fosaprepitant (30 mg/kg once daily) for 7 days. Pain threshold was assessed by the hot plate test. Expression of SP and calcitonin gene-related peptide (CGRP) in the spinal cords of these rats was evaluated by immunohistochemistry.[2] Fosaprepitant (also known as MK-0517 and L-758,298) is a water-soluble phosphoryl prodrug for aprepitant, which, when administered intravenously, is converted to aprepitant within 30 min of intravenous administration via the action of ubiquitous phosphatases. Owing to the rapid conversion of fosaprepitant to the active form (aprepitant), fosaprepitant 115 mg provided the same aprepitant exposure in terms of AUC as aprepitant 12 mg orally, and fosaprepitant is expected to provide a correspondingly similar antiemetic effect as aprepitant. Clinical studies have suggested that fosaprepitant could be appropriate as an intravenous alternative to the aprepitant oral capsule. In a study in healthy subjects, fosaprepitant 115 mg was generally well tolerated at a final drug concentration of 1 mg/ml, and fosaprepitant 115 mg was AUC bioequivalent to aprepitant 125 mg. Fosaprepitant in the dose of 115 mg has been approved by the US FDA, the EU and the Australian authorities on day 1 of a 3-day oral aprepitant regimen, with oral aprepitant administered on days 2 and 3. Fosaprepitant may be a useful parenteral alternative to oral aprepitant. Further study is needed to clarify the utility of fosaprepitant in the prevention of CINV and to clarify optimal dosing regimens that may be appropriate substitutes for oral aprepitant[2].
References	[1]. Expert Opin Investig Drugs. 2007 Dec;16(12):1977-85. [2]. 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. [3]. 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.
Additional Infomation	Fosaprepitant Dimeglumine is the dimeglumine salt form of fosaprepitant, the water-soluble, N-phosphorylated prodrug of aprepitant, with antiemetic activity. Upon intravenous administration and rapid conversion to aprepitant, this agent binds selectively to the human substance P/neurokinin 1 (NK1) receptors in the central nervous system (CNS). This inhibits receptor binding of the endogenous substance P and prevents substance P-induced emesis.

Solubility Data

Solubility (In Vitro)	H2O: ~50 mg/mL (~49.8 mM)
Solubility (In Vivo)	Solubility in Formulation 1: 100 mg/mL (99.52 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	0.9952 mL	4.9760 mL	9.9519 mL
	5 mM	0.1990 mL	0.9952 mL	1.9904 mL
	10 mM	0.0995 mL	0.4976 mL	0.9952 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.