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Record Information
Version4.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:52 UTC
Update Date2017-12-07 02:52:32 UTC
HMDB IDHMDB0015662
Secondary Accession Numbers
  • HMDB15662
Metabolite Identification
Common NameFosaprepitant
DescriptionFosaprepitant is only found in individuals that have used or taken this drug. It is an intravenously administered antiemetic drug. It is a prodrug of Aprepitant. It aids in the prevention of acute and delayed nausea and vomiting associated with chemotherapy treatment.Aprepitant has been shown in animal models to inhibit emesis induced by cytotoxic chemotherapeutic agents, such as cisplatin, via central actions. Animal and human Positron Emission Tomography (PET) studies with Aprepitant have shown that it crosses the blood brain barrier and occupies brain NK1 receptors. Animal and human studies show that Aprepitant augments the antiemetic activity of the 5-HT3-receptor antagonist ondansetron and the corticosteroid ethasone and inhibits both the acute and delayed phases of cisplatin induced emesis.In summary, the active form of fosaprepitant is as an NK1 antagonist which is because it blocks signals given off by NK1 receptors. This therefore decreases the likelihood of vomiting in patients experiencing.
Structure
Thumb
Synonyms
ValueSource
FosaprepitantumChEBI
L-758,298ChEBI
L-758298ChEBI
Emend for injectionMeSH
Fosaprepitant dimeglumineMeSH
Chemical FormulaC23H22F7N4O6P
Average Molecular Weight614.4066
Monoisotopic Molecular Weight614.116518403
IUPAC Name(3-{[(2R,3S)-2-[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-(4-fluorophenyl)morpholin-4-yl]methyl}-5-oxo-2,5-dihydro-1H-1,2,4-triazol-1-yl)phosphonic acid
Traditional Namefosaprepitant
CAS Registry Number172673-20-0
SMILES
C[C@@H](O[C@H]1OCCN(CC2=NC(=O)N(N2)P(O)(O)=O)[C@H]1C1=CC=C(F)C=C1)C1=CC(=CC(=C1)C(F)(F)F)C(F)(F)F
InChI Identifier
InChI=1S/C23H22F7N4O6P/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/h2-5,8-10,12,19-20H,6-7,11H2,1H3,(H,31,32,35)(H2,36,37,38)/t12-,19+,20-/m1/s1
InChI KeyBARDROPHSZEBKC-OITMNORJSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of chemical entities known as phenylmorpholines. These are aromatic compounds containing a morpholine ring and a benzene ring linked to each other through a CC or a CN bond.
KingdomChemical entities
Super ClassOrganic compounds
ClassOrganoheterocyclic compounds
Sub ClassOxazinanes
Direct ParentPhenylmorpholines
Alternative Parents
Substituents
  • Phenylmorpholine
  • Trifluoromethylbenzene
  • Fluorobenzene
  • Halobenzene
  • Aralkylamine
  • Aryl fluoride
  • Aryl halide
  • Monocyclic benzene moiety
  • Benzenoid
  • Azole
  • Heteroaromatic compound
  • 1,2,4-triazole
  • Tertiary aliphatic amine
  • Tertiary amine
  • Azacycle
  • Oxacycle
  • Acetal
  • Alkyl fluoride
  • Organofluoride
  • Organohalogen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Organopnictogen compound
  • Organonitrogen compound
  • Organic oxygen compound
  • Organic nitrogen compound
  • Amine
  • Alkyl halide
  • Organooxygen compound
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Ontology
Disposition

Biological Location:

  Subcellular:

  Biofluid and excreta:

Role

Industrial application:

  Pharmaceutical industry:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.0063 g/LALOGPS
logP2.89ALOGPS
logP2.4ChemAxon
logS-5ALOGPS
pKa (Strongest Acidic)1.02ChemAxon
pKa (Strongest Basic)5.69ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count9ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area123.93 ŲChemAxon
Rotatable Bond Count9ChemAxon
Refractivity138.63 m³·mol⁻¹ChemAxon
Polarizability49.92 ųChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0a4l-0469020000-a9d53cff50121f0ac397View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-014l-1291148000-89d7ce5293bc9b67d05cView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0a4l-0090120000-90a954db621c91e2b6b9View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-01pk-9640000000-5e645105fbd967a5973fView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0006-9320110000-e5a11eb20cb539f51093View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0a4l-2091220000-cdeb0047166d8b481ca8View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9130000000-4475aa8dcea01509b8ccView in MoNA
Biological Properties
Cellular Locations
  • Membrane
Biofluid Locations
  • Blood
  • Urine
Tissue LocationNot Available
PathwaysNot Available
NameSMPDB/PathwhizKEGG
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB06717 details
UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB06717 details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB06717
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID189912
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkFosaprepitant
METLIN IDNot Available
PubChem Compound219090
PDB IDNot Available
ChEBI ID64321
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General ReferencesNot Available

Enzymes

General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular weight:
57255.585
References
  1. 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. doi: 10.1586/14737140.8.11.1733. [PubMed:18983233 ]
  2. Sanchez RI, Wang RW, Newton DJ, Bakhtiar R, Lu P, Chiu SH, Evans DC, Huskey SE: Cytochrome P450 3A4 is the major enzyme involved in the metabolism of the substance P receptor antagonist aprepitant. Drug Metab Dispos. 2004 Nov;32(11):1287-92. Epub 2004 Aug 10. [PubMed:15304427 ]
General function:
Involved in monooxygenase activity
Specific function:
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine.
Gene Name:
CYP2C19
Uniprot ID:
P33261
Molecular weight:
55944.565
References
  1. 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. doi: 10.1586/14737140.8.11.1733. [PubMed:18983233 ]
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen. Participates in the bioactivation of carcinogenic aromatic and heterocyclic amines. Catalizes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin.
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular weight:
58406.915
References
  1. 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. doi: 10.1586/14737140.8.11.1733. [PubMed:18983233 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
This is a receptor for the tachykinin neuropeptide substance P. It is probably associated with G proteins that activate a phosphatidylinositol-calcium second messenger system. The rank order of affinity of this receptor to tachykinins is:substance P > substance K > neuromedin-K
Gene Name:
TACR1
Uniprot ID:
P25103
Molecular weight:
46250.5
References
  1. Poli-Bigelli S, Rodrigues-Pereira J, Carides AD, Julie Ma G, Eldridge K, Hipple A, Evans JK, Horgan KJ, Lawson F: Addition of the neurokinin 1 receptor antagonist aprepitant to standard antiemetic therapy improves control of chemotherapy-induced nausea and vomiting. Results from a randomized, double-blind, placebo-controlled trial in Latin America. Cancer. 2003 Jun 15;97(12):3090-8. [PubMed:12784346 ]
  2. Zhao MM, McNamara JM, Ho GJ, Emerson KM, Song ZJ, Tschaen DM, Brands KM, Dolling UH, Grabowski EJ, Reider PJ, Cottrell IF, Ashwood MS, Bishop BC: Practical asymmetric synthesis of aprepitant, a potent human NK-1 receptor antagonist, via a stereoselective Lewis acid-catalyzed trans acetalization reaction. J Org Chem. 2002 Sep 20;67(19):6743-7. [PubMed:12227806 ]
  3. Bergstrom M, Hargreaves RJ, Burns HD, Goldberg MR, Sciberras D, Reines SA, Petty KJ, Ogren M, Antoni G, Langstrom B, Eskola O, Scheinin M, Solin O, Majumdar AK, Constanzer ML, Battisti WP, Bradstreet TE, Gargano C, Hietala J: Human positron emission tomography studies of brain neurokinin 1 receptor occupancy by aprepitant. Biol Psychiatry. 2004 May 15;55(10):1007-12. [PubMed:15121485 ]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]