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

General Information of Drug (ID: DM72JXH)

Drug Name

Losartan Drug Info

Synonyms

Cozaar; Cozaar (TN); DUP 89; DuP 753; DuP-753; Hyzaar; JMS50MPO89; LOSARTAN POTASSIUM; Lortaan; Losartan (INN); 114798-26-4; C22H23ClN6O; CHEBI:6541; CL23623; Losartan [INN:BAN]; Losartan monopotassium salt; Losartic; Losartic (TN); MK-954; MK954; UNII-JMS50MPO89; [3H]losartan

Indication

Disease Entry	ICD 11	Status	REF
Diabetic kidney disease	GB61.Z	Approved	[1]
Hypertension	BA00-BA04	Approved	[2]
Prediabetes syndrome		Approved	[1]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 3	[3]

Therapeutic Class

Antihypertensive Agents

Cross-matching ID

PubChem CID: 3961
ChEBI ID: CHEBI:6541
CAS Number: CAS 114798-26-4
TTD Drug ID: DM72JXH
VARIDT Drug ID: DR00429
INTEDE Drug ID: DR0984
ACDINA Drug ID: D00153

Molecule(s) Related to This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Angiotensin II receptor type-1 (AGTR1)	TT8DBY3	AGTR1_HUMAN	Antagonist	[4]
HUMAN type-1 angiotensin II receptor (AGTR1)	TTPKMXQ	AGTR1_HUMAN	Blocker	[5]

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Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	Highest Status	REF
Peptide transporter 1 (SLC15A1)	DT9G7XN	S15A1_HUMAN	Approved	[6]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Approved	[7]

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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	[8]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Approved	[9]
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Approved	[10]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Approved	[8]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Approved	[11]
UDP-glucuronosyltransferase 2B7 (UGT2B7)	DEB3CV1	UD2B7_HUMAN	Approved	[9]
UDP-glucuronosyltransferase 1A10 (UGT1A10)	DEL5N6Y	UD110_HUMAN	Approved	[9]
UDP-glucuronosyltransferase 1A3 (UGT1A3)	DEF2WXN	UD13_HUMAN	Approved	[9]

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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
Angiotensin II receptor type-1 (AGTR1)	DTT	AGTR1	9.315	6.241	6.761	5.625
P-glycoprotein 1 (ABCB1)	DTP	P-GP	7.009	6.988	7.442	8.135
Peptide transporter 1 (SLC15A1)	DTP	PEPT1	3.807	4.52	5.285	7.133
Cytochrome P450 2C8 (CYP2C8)	DME	CYP2C8	9.791	3.744	3.413	1.609
Cytochrome P450 3A5 (CYP3A5)	DME	CYP3A5	10.08	7.207	5.403	9.211
Cytochrome P450 2C9 (CYP2C9)	DME	CYP2C9	11.76	5.931	6.164	9.423
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

Diabetic kidney disease

ICD Disease Classification

GB61.Z

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Angiotensin II receptor type-1 (AGTR1)	DTT	AGTR1	8.95E-01	1.34E-02	0.07
P-glycoprotein 1 (ABCB1)	DTP	P-GP	9.39E-02	1.07E-01	2.80E-01
Peptide transporter 1 (SLC15A1)	DTP	PEPT1	4.57E-01	2.15E-02	1.72E-01
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DME	UGT1A1	1.10E-01	-5.91E-02	-3.60E-01
Cytochrome P450 2C8 (CYP2C8)	DME	CYP2C8	1.82E-04	-1.35E-01	-5.84E-01
Cytochrome P450 3A5 (CYP3A5)	DME	CYP3A5	9.96E-01	-3.17E-03	-1.84E-02
Cytochrome P450 2C9 (CYP2C9)	DME	CYP2C9	1.90E-01	-9.81E-03	-5.96E-02
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	1.04E-02	6.29E-02	3.54E-01

Molecular Expression Atlas between Disease Section and Healthy Individual Tissue

References

1	Losartan FDA Label
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: 590).
3	ClinicalTrials.gov (NCT04343001) Coronavirus Response - Active Support for Hospitalised Covid-19 Patients. U.S. National Institutes of Health.
4	Radioligand binding assays: application of [(125)I]angiotensin II receptor binding. Methods Mol Biol. 2009;552:131-41.
5	Controversies of renin-angiotensin system inhibition during the COVID-19 pandemic. Nat Rev Nephrol. 2020 Apr 3.
6	High-affinity interaction of sartans with H+/peptide transporters. Drug Metab Dispos. 2009 Jan;37(1):143-9.
7	Active transport of the angiotensin-II antagonist losartan and its main metabolite EXP 3174 across MDCK-MDR1 and caco-2 cell monolayers. Br J Pharmacol. 2000 Mar;129(6):1235-43.
8	Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
9	Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
10	The human UDP-glucuronosyltransferase UGT1A3 is highly selective towards N2 in the tetrazole ring of losartan, candesartan, and zolarsartan. Biochem Pharmacol. 2008 Sep 15;76(6):763-72.
11	Drug-drug interaction between losartan and paclitaxel in human liver microsomes with different CYP2C8 genotypes. Basic Clin Pharmacol Toxicol. 2015 Jun;116(6):493-8.