Details of the Drug-Related molecule(s) Expression Atlas

General Information of Drug (ID: DM053KT)

Drug Name

Aprepitant Drug Info

Synonyms

Aprepitant [USAN]; L 754030; MK 0869; Emend (TN); L-754030; MK-0869; ONO-7436; Aprepitant (JAN/USAN/INN); MK-869, L-754030, Emend, Aprepitant; 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; 3-(((2R,3S)-3-(p-Fluorophenyl)-2-(((alphaR)-alpha-methyl-3,5-bis(trifluoromethyl)benzyl)oxy)morpholino)methyl)-delta(sup 2)-1,2,4-triazolin-5-one; 5-[[(2R,3S)-2-[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-(4-fluorophenyl)morpholin-4-yl]methyl]-1,2-dihydro-1,2,4-triazol-3-one; 5-[[(2S,3R)-2-[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-(4-fluorophenyl)morpholin-4-yl]methyl]-1,2-dihydro-1,2,4-triazol-3-one; 5-{[(2R,3S)-2-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy}-3-(4-fluorophenyl)morpholin-4-yl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one

Indication

Disease Entry	ICD 11	Status	REF
Depression	6A70-6A7Z	Approved	[1]
Nausea	MD90	Approved	[2]
Vomiting	MD90	Approved	[3]
Solid tumour/cancer	2A00-2F9Z	Phase 3	[4]

Therapeutic Class

Antiemetics

Cross-matching ID

PubChem CID: 135413536
ChEBI ID: CHEBI:499361
CAS Number: CAS 170729-80-3
TTD Drug ID: DM053KT
VARIDT Drug ID: DR01398
INTEDE Drug ID: DR0125
ACDINA Drug ID: D00042

Molecule(s) Related to This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Substance-P receptor (TACR1)	TTZPO1L	NK1R_HUMAN	Antagonist	[5]

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Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	Highest Status	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Approved	[6]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	Highest Status	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Approved	[7]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Approved	[8]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Approved	[8]

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The Expression Level of Molecule(s) in Normal Tissue of Major ADME-Related Organs

Molecule	Molecule Type	Gene Name	Liver	Colon	Kidney	Small Intestine
Substance-P receptor (TACR1)	DTT	TACR1	3.597	4.186	4.271	5.113
P-glycoprotein 1 (ABCB1)	DTP	P-GP	7.009	6.988	7.442	8.135
Cytochrome P450 1A2 (CYP1A2)	DME	CYP1A2	10.036	5.779	6.508	6.481
Mephenytoin 4-hydroxylase (CYP2C19)	DME	CYP2C19	7.867	5.142	5.52	7.08
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	11.692	6.58	4.984	9.089

Molecule Expression Atlas in Normal Tissue of Major ADME-related organs

The Expression Level of Molecule(s) between Disease Section and Healthy Individual Tissue

The Studied Disease

Depression

ICD Disease Classification

6A70-6A7Z

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Substance-P receptor (TACR1)	DTT	TACR1	7.40E-01	0.02	0.07
Substance-P receptor (TACR1)	DTT	TACR1	8.57E-01	-0.02	-0.18
P-glycoprotein 1 (ABCB1)	DTP	P-GP	1.19E-01	-1.32E-01	-2.77E-01
P-glycoprotein 1 (ABCB1)	DTP	P-GP	1.65E-01	-1.47E-01	-4.48E-01
Cytochrome P450 1A2 (CYP1A2)	DME	CYP1A2	6.73E-02	6.49E-02	3.07E-01
Cytochrome P450 1A2 (CYP1A2)	DME	CYP1A2	6.45E-01	2.07E-02	1.74E-01
Mephenytoin 4-hydroxylase (CYP2C19)	DME	CYP2C19	7.39E-01	1.54E-02	4.74E-02
Mephenytoin 4-hydroxylase (CYP2C19)	DME	CYP2C19	4.64E-02	-8.21E-02	-7.11E-01
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	4.66E-01	4.25E-02	1.20E-01
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	4.75E-01	5.15E-02	3.64E-01

Molecular Expression Atlas between Disease Section and Healthy Individual Tissue

References

1	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
2	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 3490).
3	Aprepitant FDA Label
4	ClinicalTrials.gov (NCT00571168) Efficacy and Safety of Aprepitant in Subjects With Multiple Myeloma During and After High-dose Chemotherapy. U.S. National Institutes of Health.
5	Potent, brain-penetrant, hydroisoindoline-based human neurokinin-1 receptor antagonists. J Med Chem. 2009 May 14;52(9):3039-46.
6	Improving the prediction of the brain disposition for orally administered drugs using BDDCS. Adv Drug Deliv Rev. 2012 Jan;64(1):95-109.
7	Lack of effect of aprepitant on the pharmacokinetics of docetaxel in cancer patients. Cancer Chemother Pharmacol. 2005 Jun;55(6):609-16.
8	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.