Identification

Name
Aprepitant
Accession Number
DB00673  (APRD00100)
Type
Small Molecule
Groups
Approved, Investigational
Description

Aprepitant, an antiemetic, is a substance P/neurokinin 1 (NK1) receptor antagonist which, in combination with other antiemetic agents, is indicated for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy. Aprepitant is a selective high-affinity antagonist of human substance P/neurokinin 1 (NK1) receptors. Aprepitant has little or no affinity for serotonin (5-HT3), dopamine, and corticosteroid receptors, the targets of existing therapies for chemotherapy-induced nausea and vomiting (CI NV).

Structure
Thumb
Synonyms
  • 3-(((2R,3S)-3-(P-Fluorophenyl)-2-(((alphar)-alpha-methyl-3,5-bis(trifluoromethyl)benzyl)oxy)morpholino)methyl)-delta(2)-1,2,4-triazolin-5-one
  • Aprepitant
  • Aprépitant
  • Aprepitantum
External IDs
L 754030 / L-754939 / MK-0869 / MK-869
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CinvantiInjection, emulsion130 mg/18mLIntravenousHeron Therapeutics2018-01-03Not applicableUs
EmendCapsule40 mg/1OralMerck Sharp & Dohme Limited2003-03-26Not applicableUs00006 0464 05 nlmimage10 4039a01d
EmendCapsule80 mgOralMerck Sharp & Dohme B.V.2003-11-11Not applicableEu
EmendCapsule80 mgOralMerck Ltd.2007-09-24Not applicableCanada
EmendCapsule40 mg/1OralRebel Distributors2003-03-26Not applicableUs
EmendPowder, for suspension125 mgOralMerck Sharp & Dohme B.V.2003-11-11Not applicableEu
EmendCapsule40 mgOralMerck Sharp & Dohme B.V.2003-11-11Not applicableEu
EmendCapsule125 mgOralMerck Sharp & Dohme B.V.2003-11-11Not applicableEu
EmendCapsule125 mg/1OralMerck Sharp & Dohme Limited2003-03-26Not applicableUs
EmendCapsule80 mgOralMerck Sharp & Dohme B.V.2003-11-11Not applicableEu
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
AprepitantCapsule40 mg/1OralGlenmark Pharmaceuticals Inc.,Usa2017-10-12Not applicableUs
AprepitantCapsule40 mg/1OralSandoz2016-12-27Not applicableUs
AprepitantCapsule125 mg/1OralGlenmark Pharmaceuticals Inc.,Usa2017-10-12Not applicableUs
AprepitantCapsule125 mg/1OralSandoz2016-12-27Not applicableUs
AprepitantCapsule80 mg/1OralGlenmark Pharmaceuticals Inc.,Usa2017-10-12Not applicableUs
AprepitantCapsule80 mg/1OralSandoz2016-12-27Not applicableUs
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
AprepitantAprepitant (80 mg/1) + Aprepitant (125 mg/1)KitGlenmark Pharmaceuticals Inc.,Usa2017-10-12Not applicableUs
AprepitantAprepitant (80 mg/1) + Aprepitant (125 mg/1)KitSandoz2016-12-27Not applicableUs
AprepitantAprepitant (80 mg/1) + Aprepitant (125 mg/1)KitGlenmark Pharmaceuticals Inc.,Usa2017-10-12Not applicableUs
AprepitantAprepitant (80 mg/1) + Aprepitant (125 mg/1)KitSandoz2016-12-27Not applicableUs
EmendAprepitant (80 mg/1) + Aprepitant (125 mg/1)KitPhysicians Total Care, Inc.2005-06-24Not applicableUs
EmendAprepitant (80 mg/1) + Aprepitant (125 mg/1)KitMerck Sharp & Dohme Limited2003-03-26Not applicableUs
EmendAprepitant (80 mg/1) + Aprepitant (125 mg/1)KitPhysicians Total Care, Inc.2005-06-24Not applicableUs
EmendAprepitant (80 mg/1) + Aprepitant (125 mg/1)KitMerck Sharp & Dohme Limited2003-03-26Not applicableUs
Emend Tri-packAprepitant (125 mg) + Aprepitant (80 mg)Capsule; KitOralMerck Ltd.2007-09-24Not applicableCanada
Emend Tri-packAprepitant (125 mg) + Aprepitant (80 mg)Capsule; KitOralMerck Ltd.2007-09-24Not applicableCanada
International/Other Brands
Aprecap (Glenmark)
Categories
UNII
1NF15YR6UY
CAS number
170729-80-3
Weight
Average: 534.4267
Monoisotopic: 534.150187993
Chemical Formula
C23H21F7N4O3
InChI Key
ATALOFNDEOCMKK-OITMNORJSA-N
InChI
InChI=1S/C23H21F7N4O3/c1-12(14-8-15(22(25,26)27)10-16(9-14)23(28,29)30)37-20-19(13-2-4-17(24)5-3-13)34(6-7-36-20)11-18-31-21(35)33-32-18/h2-5,8-10,12,19-20H,6-7,11H2,1H3,(H2,31,32,33,35)/t12-,19+,20-/m1/s1
IUPAC Name
3-{[(2R,3S)-2-[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-(4-fluorophenyl)morpholin-4-yl]methyl}-4,5-dihydro-1H-1,2,4-triazol-5-one
SMILES
C[C@@H](O[C@H]1OCCN(CC2=NNC(=O)N2)[C@H]1C1=CC=C(F)C=C1)C1=CC(=CC(=C1)C(F)(F)F)C(F)(F)F

Pharmacology

Indication

For the prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy, including high-dose cisplatin (in combination with other antiemetic agents).

Associated Conditions
Pharmacodynamics

Aprepitant, an antiemetic, is a substance P/neurokinin 1 (NK1) receptor antagonist which, in combination with other antiemetic agents, is indicated for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy. Aprepitant is a selective high-affinity antagonist of human substance P/neurokinin 1 (NK1) receptors. Aprepitant has little or no affinity for serotonin (5-HT3), dopamine, and corticosteroid receptors, the targets of existing therapies for chemotherapy-induced nausea and vomiting (CI NV).

Mechanism of action

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.

TargetActionsOrganism
ASubstance-P receptor
antagonist
Human
Absorption

The mean absolute oral bioavailability of aprepitant is approximately 60 to 65%.

Volume of distribution
  • 70 L
Protein binding

>95%

Metabolism

Aprepitant is metabolized primarily by CYP3A4 with minor metabolism by CYP1A2 and CYP2C19. Seven metabolites of aprepitant, which are only weakly active, have been identified in human plasma.

Route of elimination

Aprepitant is eliminated primarily by metabolism; aprepitant is not renally excreted. Aprepitant is excreted in the milk of rats. It is not known whether this drug is excreted in human milk.

Half life

9-13 hours

Clearance
  • Apparent plasma cl=62-90 mL/min
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of Aprepitant can be decreased when combined with (R)-warfarin.
(S)-WarfarinThe metabolism of Aprepitant can be decreased when combined with (S)-Warfarin.
16-BromoepiandrosteroneThe metabolism of Aprepitant can be decreased when combined with 16-Bromoepiandrosterone.
3,5-diiodothyropropionic acidThe metabolism of Aprepitant can be decreased when combined with 3,5-diiodothyropropionic acid.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Aprepitant.
5-androstenedioneThe metabolism of Aprepitant can be decreased when combined with 5-androstenedione.
6-Deoxyerythronolide BThe metabolism of Aprepitant can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of Aprepitant can be decreased when combined with 6-O-benzylguanine.
AbemaciclibThe metabolism of Aprepitant can be decreased when combined with Abemaciclib.
AbirateroneThe metabolism of Aprepitant can be decreased when combined with Abiraterone.
Food Interactions
  • Take without regard to meals.

References

Synthesis Reference

Mangesh Shivram Sawant, Girish Dixit, Nitin Sharad Chandra Pradhan, Mubeen Ahmad Khan, Sukumar Sinha, "Amorphous and Crystalline Forms of Aprepitant and Processes for the Preparation Thereof." U.S. Patent US20090192161, issued July 30, 2009.

US20090192161
General References
Not Available
External Links
Human Metabolome Database
HMDB0014811
PubChem Compound
6918365
PubChem Substance
46505211
ChemSpider
5293568
BindingDB
50220136
ChEBI
499361
ChEMBL
CHEMBL1471
Therapeutic Targets Database
DNC000952
PharmGKB
PA164747039
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Aprepitant
ATC Codes
A04AD12 — Aprepitant
AHFS Codes
  • 56:22.32 — Neurokinin-1 Receptor Antagonists
FDA label
Download (293 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedSupportive CareNausea / Vomiting1
1Active Not RecruitingTreatmentGlioblastomas1
1Active Not RecruitingTreatmentHealthy Volunteers1
1CompletedSupportive CareChemotherapy-Induced Nausea and Vomiting (CINV)1
1CompletedTreatmentCancer, Breast / Nausea and vomiting1
1CompletedTreatmentChemotherapy-Induced Nausea and Vomiting (CINV)2
1CompletedTreatmentChemotherapy-Induced Nausea and Vomiting (CINV) / Post-Operative Nausea and Vomiting (PONV)1
1CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections3
1CompletedTreatmentMultiple Myeloma (MM) / Non-Hodgkin's Lymphoma (NHL) / Tumors, Solid1
1CompletedTreatmentOpioid Dependence1
1CompletedTreatmentPost-Operative Nausea and Vomiting (PONV)1
1TerminatedTreatmentChemotherapy-Induced Nausea and Vomiting (CINV)1
1Unknown StatusTreatmentHeroin Dependence / Opioid-Related Disorders / Substance-Related Disorders1
2Active Not RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
2CompletedPreventionLeukemia Acute Myeloid Leukemia (AML)1
2CompletedSupportive CareColorectal Cancers / Nausea and vomiting1
2CompletedSupportive CareExtrahepatic Bile Duct Cancer / Nausea / Stage II Pancreatic Cancer / Stage III Pancreatic Cancer / Stage IV Pancreatic Cancer / Vomiting1
2CompletedSupportive CareItching1
2CompletedSupportive CareMalignant Lymphomas / Myeloma, Plasma-Cell1
2CompletedSupportive CareNausea / Vomiting1
2CompletedTreatmentAcute Myelogenous Leukaemia (AML) / Chronic Chronic myelogenous leukemia / Hematologic Diseases / Myelodysplastic Syndrome1
2CompletedTreatmentAlcohol Dependence / Alcohol Use Disorder (AUD) / Cannabis Dependence / Cannabis Use Disorders1
2CompletedTreatmentAlcohol Dependence / Alcoholism / Posttraumatic Stress Disorders1
2CompletedTreatmentCancer of the Ovary / Chemotherapy-Induced Nausea and Vomiting (CINV)1
2CompletedTreatmentCannabis Dependence1
2CompletedTreatmentChemotherapy-Induced Nausea and Vomiting (CINV)1
2CompletedTreatmentChemotherapy-Induced / Nausea and vomiting1
2CompletedTreatmentGliomas / Nausea / Vomiting1
2CompletedTreatmentNausea / Vomiting2
2CompletedTreatmentPost-Operative Nausea / Post-Operative Vomiting1
2CompletedTreatmentPruritus1
2Not Yet RecruitingSupportive CareChemotherapy-Induced Nausea and Vomiting (CINV) / Lung Cancers1
2Not Yet RecruitingTreatmentChemotherapy-Induced Nausea and Vomiting (CINV)1
2Not Yet RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC) / Nausea / Vomiting1
2RecruitingPreventionChemotherapy Induced Neutropenia / Colo-rectal Cancer1
2RecruitingTreatmentChemotherapy-Induced Nausea and Vomiting (CINV) / Head Neck Cancer / Vomiting1
2RecruitingTreatmentChemotherapy-Induced Nausea and Vomiting (CINV) / Nausea / Vomiting1
2TerminatedPreventionNausea / Vomiting1
2TerminatedTreatmentAlcohol Dependence / Cocaine1
2TerminatedTreatmentChemotherapy-Induced Nausea and Vomiting (CINV)1
2TerminatedTreatmentCancer treatment / Nausea / Vomiting1
2Unknown StatusPreventionPost-Operative Nausea and Vomiting (PONV) / Tumors, Solid1
2Unknown StatusSupportive CareChemotherapy-Induced Nausea and Vomiting (CINV)2
2, 3CompletedPreventionPost-Operative Nausea and Vomiting (PONV)1
3CompletedPreventionChemotherapy-Induced Nausea and Vomiting (CINV)6
3CompletedPreventionPost-Operative Nausea and Vomiting (PONV)2
3CompletedPreventionVomiting1
3CompletedSupportive CareGerm Cell Tumors1
3CompletedSupportive CareNausea1
3CompletedTreatmentChemotherapy-Induced Nausea and Vomiting (CINV)1
3CompletedTreatmentGastroparesis1
3CompletedTreatmentMajor Depressive Disorder (MDD)9
3Not Yet RecruitingSupportive CareChemotherapy-Induced Nausea and Vomiting (CINV)1
3Not Yet RecruitingSupportive CareChemotherapy-Induced Nausea and Vomiting (CINV) / Colorectal Cancers1
3Not Yet RecruitingSupportive CareNausea / Vomiting1
3RecruitingPreventionCancer, Breast1
3RecruitingPreventionChemotherapy Induced Vomiting / Leukemia Acute Myeloid Leukemia (AML)1
3RecruitingPreventionChemotherapy-Induced Nausea and Vomiting (CINV)1
3RecruitingPreventionChildhood Cancers / Nausea / Vomiting1
3RecruitingSupportive CareChemotherapy-Induced Nausea and Vomiting (CINV)1
3RecruitingTreatmentNon-Small Cell Lung Carcinoma (NSCLC)1
3TerminatedPreventionChemotherapy-Induced Nausea and Vomiting (CINV)1
3TerminatedTreatmentVomiting2
3Unknown StatusPreventionNausea / Vomiting1
3Unknown StatusTreatmentMultiple Myeloma (MM)1
4Active Not RecruitingTreatmentVomiting2
4CompletedNot AvailableHealthy Volunteers1
4CompletedPreventionNausea / Postoperative Nausea and Vomiting (PONV)1
4CompletedPreventionPost-Operative Nausea and Vomiting (PONV)6
4CompletedSupportive CareCancers / Tumors1
4CompletedTreatmentCancer of the Ovary / Uterine Cancers1
4CompletedTreatmentCancer, Breast1
4CompletedTreatmentLeukemias / Malignant Lymphomas1
4CompletedTreatmentNausea / Vomiting1
4RecruitingPreventionLaparoscopic Sleeve Gastrectomy / Post-Operative Nausea and Vomiting (PONV)1
4RecruitingPreventionPost-Operative Nausea and Vomiting (PONV)1
4TerminatedPreventionPost-Operative Nausea and Vomiting (PONV)1
4TerminatedTreatmentPruritus / Sezary Syndrome1
4TerminatedTreatmentTumors1
4Unknown StatusPreventionLeukemias / Malignant Lymphomas1
4WithdrawnTreatmentNausea / Vomiting1
Not AvailableActive Not RecruitingNot AvailableLung Cancer Non-Small Cell Cancer (NSCLC)1
Not AvailableActive Not RecruitingSupportive CareChemotherapy-Induced Nausea and Vomiting (CINV) / Gastrointestinal Cancers1
Not AvailableCompletedNot AvailableChemotherapy-Induced Nausea and Vomiting (CINV)1
Not AvailableCompletedBasic ScienceChronic Obstructive Pulmonary Disease (COPD)2
Not AvailableCompletedBasic ScienceNarcotic Abuse1
Not AvailableCompletedPreventionNausea / Vomiting1
Not AvailableCompletedPreventionPost-Operative Nausea and Vomiting (PONV)3
Not AvailableCompletedSupportive CareCancer of the Ovary / Cancer, Breast / Chronic Myeloproliferative Disorders / Gestational Trophoblastic Disease / Leukemias / Malignant Lymphomas / Multiple Myeloma and Plasma Cell Neoplasm / Myelodysplastic Syndromes / Myelodysplastic/Myeloproliferative Neoplasms / Nausea and vomiting / Neuroblastomas / Testicular germ cell tumour1
Not AvailableCompletedSupportive CareCancers1
Not AvailableCompletedSupportive CareNausea / Vomiting1
Not AvailableCompletedSupportive CareNeoplasms, Malignant1
Not AvailableCompletedTreatmentMalignant Lymphomas1
Not AvailableCompletedTreatmentNausea / Vomiting1
Not AvailableCompletedTreatmentPancreatitis1
Not AvailableRecruitingTreatmentCognitive Dysfunctions1
Not AvailableRecruitingTreatmentHigh Blood Pressure (Hypertension) / Type 2 Diabetes Mellitus1
Not AvailableTerminatedSupportive CareMalignant Digestive System Neoplasm / Nausea and vomiting1
Not AvailableTerminatedSupportive CareMalignant Ovarian Mixed Epithelial Tumor / Nausea and vomiting / Ovarian Brenner Tumor / Ovarian Clear Cell Cystadenocarcinoma / Ovarian Endometrioid Adenocarcinoma / Ovarian Mucinous Cystadenocarcinoma / Ovarian Seromucinous Carcinoma / Ovarian Serous Cystadenocarcinoma / Stage II Ovarian Cancer / Stage IIA Fallopian Tube Cancer / Stage IIA Ovarian Cancer / Stage IIB Fallopian Tube Cancer / Stage IIB Ovarian Cancer / Stage IIC Fallopian Tube Cancer / Stage IIC Ovarian Cancer / Stage IIIA Fallopian Tube Cancer / Stage IIIA Ovarian Cancer / Stage IIIA Primary Peritoneal Cancer / Stage IIIB Fallopian Tube Cancer / Stage IIIB Ovarian Cancer / Stage IIIB Primary Peritoneal Cancer / Stage IIIC Fallopian Tube Cancer / Stage IIIC Ovarian Cancer / Stage IIIC Primary Peritoneal Cancer / Stage IV Fallopian Tube Cancer / Stage IV Ovarian Cancer / Stage IV Primary Peritoneal Cancer / Undifferentiated Ovarian Carcinoma1
Not AvailableUnknown StatusPreventionColorectal Cancers1
Not AvailableUnknown StatusPreventionNausea / Vomiting1
Not AvailableUnknown StatusSupportive CareNon-Hodgkin's Lymphoma (NHL)1
Not AvailableWithdrawnPreventionCancer of the Ovary1
Not AvailableWithdrawnPreventionPolymorphism, Genetic / Post-Operative Nausea and Vomiting (PONV)1
Not AvailableWithdrawnPreventionPost-Operative Nausea and Vomiting (PONV)2
Not AvailableWithdrawnSupportive CareLeukemias / Lymphoproliferative Disorders / Malignant Lymphomas / Multiple Myeloma and Plasma Cell Neoplasm / Myelodysplastic Syndromes / Myeloproliferative Disorders / Nausea and vomiting / Tumors, Solid1

Pharmacoeconomics

Manufacturers
  • Merck and co inc
Packagers
  • Merck & Co.
  • Physicians Total Care Inc.
Dosage forms
FormRouteStrength
Injection, emulsionIntravenous130 mg/18mL
CapsuleOral125 mg/1
CapsuleOral125 mg
CapsuleOral165 mg
CapsuleOral40 mg
CapsuleOral40 mg/1
CapsuleOral80 mg
CapsuleOral80 mg/1
Kit
Powder, for suspensionOral125 mg
Powder, for suspensionOral125 mg/1
Capsule; kitOral
Prices
Unit descriptionCostUnit
Emend 6 125 mg capsule Box1046.01USD box
Emend 6 80 mg capsule Box678.62USD box
Emend 5 80 mg capsule Box553.13USD box
Emend 3 80 & 125 mg capsule Disp Pack415.76USD disp
Emend 115 mg Solution 1 Vial = 10ml242.13USD vial
Emend 115 mg vial232.82USD vial
Emend 2 80 mg capsule Disp Pack226.21USD disp
Emend 125 mg capsule161.34USD capsule
Emend 80 mg capsule108.76USD capsule
Emend 40 mg capsule Box58.17USD box
Emend 40 mg capsule55.89USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5145684No1994-01-252011-01-25Us
CA2469315No2008-12-022022-12-19Canada
US8258132No2007-09-262027-09-26Us
US6096742No1998-07-012018-07-01Us
US9561229No2015-09-182035-09-18Us
US9808465No2015-09-182035-09-18Us
US9974794No2015-09-182035-09-18Us
US9974793No2015-09-182035-09-18Us
US9974742No2015-09-182035-09-18Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityPractically insolubleNot Available
logP4.5Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0194 mg/mLALOGPS
logP2.44ALOGPS
logP5.22ChemAxon
logS-4.4ALOGPS
pKa (Strongest Acidic)9.65ChemAxon
pKa (Strongest Basic)3.51ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area75.19 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity116.93 m3·mol-1ChemAxon
Polarizability45.56 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9952
Blood Brain Barrier+0.5588
Caco-2 permeable-0.6237
P-glycoprotein substrateSubstrate0.8106
P-glycoprotein inhibitor IInhibitor0.5243
P-glycoprotein inhibitor IINon-inhibitor0.9564
Renal organic cation transporterNon-inhibitor0.7444
CYP450 2C9 substrateNon-substrate0.788
CYP450 2D6 substrateNon-substrate0.9115
CYP450 3A4 substrateSubstrate0.6461
CYP450 1A2 substrateNon-inhibitor0.6012
CYP450 2C9 inhibitorNon-inhibitor0.535
CYP450 2D6 inhibitorNon-inhibitor0.84
CYP450 2C19 inhibitorNon-inhibitor0.5862
CYP450 3A4 inhibitorInhibitor0.5
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8396
Ames testNon AMES toxic0.5758
CarcinogenicityNon-carcinogens0.8152
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.6055 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.6598
hERG inhibition (predictor II)Inhibitor0.8163
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds 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.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Oxazinanes
Sub Class
Morpholines
Direct Parent
Phenylmorpholines
Alternative Parents
Trifluoromethylbenzenes / Fluorobenzenes / Aralkylamines / Aryl fluorides / Triazoles / Heteroaromatic compounds / Trialkylamines / Oxacyclic compounds / Azacyclic compounds / Acetals
show 5 more
Substituents
Phenylmorpholine / Trifluoromethylbenzene / Fluorobenzene / Halobenzene / Aralkylamine / Aryl fluoride / Aryl halide / Monocyclic benzene moiety / Benzenoid / Azole
show 20 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
morpholines, triazoles, (trifluoromethyl)benzenes, cyclic acetal (CHEBI:499361)

Targets

Details
1. Substance-P receptor
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Tachykinin receptor activity
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 aff...
Gene Name
TACR1
Uniprot ID
P25103
Uniprot Name
Substance-P receptor
Molecular Weight
46250.5 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  2. Brands KM, Payack JF, Rosen JD, Nelson TD, Candelario A, Huffman MA, Zhao MM, Li J, Craig B, Song ZJ, Tschaen DM, Hansen K, Devine PN, Pye PJ, Rossen K, Dormer PG, Reamer RA, Welch CJ, Mathre DJ, Tsou NN, McNamara JM, Reider PJ: Efficient synthesis of NK(1) receptor antagonist aprepitant using a crystallization-induced diastereoselective transformation. J Am Chem Soc. 2003 Feb 26;125(8):2129-35. [PubMed:12590540]
  3. Rodgers J, Bradley B, Kennedy PG: Combination chemotherapy with a substance P receptor antagonist (aprepitant) and melarsoprol in a mouse model of human African trypanosomiasis. Parasitol Int. 2007 Dec;56(4):321-4. Epub 2007 Jun 29. [PubMed:17643344]
  4. 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]
  5. 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]
  6. 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]

Enzymes

Details
1. Cytochrome P450 3A4
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Vitamin d3 25-hydroxylase 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 react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  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]
  3. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Oxygen binding
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 un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Oxygen binding
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 un...
Gene Name
CYP3A7
Uniprot ID
P24462
Uniprot Name
Cytochrome P450 3A7
Molecular Weight
57525.03 Da
References
  1. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase 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 im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. 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]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
Inducer
General Function
Steroid hydroxylase 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 un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Dando TM, Perry CM: Aprepitant: a review of its use in the prevention of chemotherapy-induced nausea and vomiting. Drugs. 2004;64(7):777-94. [PubMed:15025555]
  2. Navari RM: Aprepitant: a neurokinin-1 receptor antagonist for the treatment of chemotherapy-induced nausea and vomiting. Expert Rev Anticancer Ther. 2004 Oct;4(5):715-24. doi: 10.1586/14737140.4.5.715. [PubMed:15485308]
  3. Aprepitant FDA label [File]

Drug created on June 13, 2005 07:24 / Updated on October 15, 2018 04:36