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

General Information of Drug (ID: DMB39LO)

• Drug Name: Metolazone Drug Info
• Synonyms: Diulo; Metalazone; Metalozone; Metenix; Metolazona; Metolazonum; Microx; Mykrox; Oldren; Xuret; Zaroxolyn; Metolazona [INN-Spanish]; Metolazonum [INN-Latin]; Mykrox (TN); SR 720-22; Zaroxolyn (TN); SR-720-22; Metolazone (JAN/USP/INN); Metolazone [USAN:BAN:INN:JAN]; Mykrox, Zaroxolyn, Diulo, Metolazone; 2-Methyl-3-o-tolyl-6-sulfamyl-7-chloro-1,2,3,4-tetrahydro-4-quinazolinone; 7-Chloro-1,2,3,4-tetrahydro-2-methyl-3-(2-methylphenyl)-4-oxo-6-quinazolinesulfonamide; 7-Chloro-1,2,3,4-tetrahydro-2-methyl-4-oxo-3-o-tolyl-6-quinazolinesulfonamide; 7-chloro-2-methyl-3-(2-methylphenyl)-4-oxo-1,2-dihydroquinazoline-6-sulfonamide

Indication

Disease Entry	ICD 11	Status	REF
Edema	MG29	Approved	[1]
Hypertension	BA00-BA04	Approved	[1]

• Therapeutic Class: Antihypertensive Agents
• Cross-matching ID:
  PubChem CID: 4170
  ChEBI ID: CHEBI:64354
  CAS Number: CAS 17560-51-9
  TTD Drug ID: DMB39LO
  VARIDT Drug ID: DR01032
  ACDINA Drug ID: D00423

Molecule-Related Drug Atlas

Drug(s) Targeting Solute carrier family 12 member 3 (SLC12A3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Bendroflumethiazide	DM7EVLC	High blood pressure	BA00	Approved	[6]
Polythiazide	DMCH80F	Edema	MG29	Approved	[2]

Drug(s) Transported By Thiazide-sensitive sodium-chloride cotransporter (SLC12A3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Bumetanide	DMRV7H0	Congestive heart failure	BD10	Approved	[7]

Drug(s) Affected By Nuclear receptor subfamily 1 group I member 2 (NR1I2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[5]
Vidarabine	DM0N85H	Hepatosplenic T-cell lymphoma		Approved	[5]
Beta-carotene	DM0RXBT	Vitamin deficiency	5B55-5B71	Approved	[8]
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[9]
Secobarbital	DM14RF5	Epilepsy	8A60-8A68	Approved	[10]
Etidronic acid	DM1XHYJ	Bone Paget disease		Approved	[5]
Tiaprofenic acid	DM23D7J	Osteoarthritis	FA00-FA05	Approved	[5]
Bromperidol	DM24XYQ	Schizophrenia	6A20	Approved	[5]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[11]
Deoxycholic acid	DM3GYAL	Subcutaneous fat disorder	EF02	Approved	[12]

Drug(s) Affected By HLA class I histocompatibility antigen, B alpha chain (HLA-B)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Carbamazepine	DMZOLBI	Epilepsy	8A60-8A68	Approved	[13]
Phenytoin	DMNOKBV	Epilepsy	8A60-8A68	Approved	[14]
Allopurinol	DMLPAOB	Gout	FA25	Approved	[15]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[16]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[17]
Phenobarbital	DMXZOCG	Cluster headache	8A81.0	Approved	[18]
Amoxicillin	DMUYNEI	Acute otitis media	AB00	Approved	[4]
Abacavir	DMMN36E	Human immunodeficiency virus infection	1C62	Approved	[19]
Flucloxacillin	DMNUWST	Bacterial infection	1A00-1C4Z	Approved	[20]
Aspirin	DM672AH	Acute coronary syndrome	BA41	Approved	[21]

Drug(s) Affected By HLA class II histocompatibility antigen, DQ beta 2 chain (HLA-DQB2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Isotretinoin	DM4QTBN	Acne vulgaris	ED80	Approved	[22]
Benzo(a)pyrene	DMN7J43	N. A.	N. A.	Phase 1	[23]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Solute carrier family 12 member 3 (SLC12A3)	TTP362L	S12A3_HUMAN	Blocker	[2]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Thiazide-sensitive sodium-chloride cotransporter (SLC12A3)	DT6MDC9	S12A3_HUMAN	Substrate	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
HLA class I histocompatibility antigen, B alpha chain (HLA-B)	OTNXFWY2	HLAB_HUMAN	Gene/Protein Processing	[4]
HLA class II histocompatibility antigen, DQ beta 2 chain (HLA-DQB2)	OTZYAIBF	DQB2_HUMAN	Gene/Protein Processing	[4]
Nuclear receptor subfamily 1 group I member 2 (NR1I2)	OTC5U0N5	NR1I2_HUMAN	Gene/Protein Processing	[5]

References

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• [2] The renal thiazide-sensitive Na-Cl cotransporter as mediator of the aldosterone-escape phenomenon. J Clin Invest. 2001 Jul;108(2):215-22.
• [3] Inhibition of binding of [3H]metolazone to rat kidney membrane by stilbene disulfonates. Biochem Pharmacol. 1991 Jun 1;41(11):1745-50.
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• [9] Lignans, bacteriocides and organochlorine compounds activate the human pregnane X receptor (PXR). Toxicol Appl Pharmacol. 2005 Dec 1;209(2):123-33. doi: 10.1016/j.taap.2005.03.015.
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• [11] Identification of HMG-CoA reductase inhibitors as activators for human, mouse and rat constitutive androstane receptor. Drug Metab Dispos. 2005 Jul;33(7):924-9.
• [12] Acetylated deoxycholic (DCA) and cholic (CA) acids are potent ligands of pregnane X (PXR) receptor. Toxicol Lett. 2017 Jan 4;265:86-96.
• [13] Carbamazepine, HLA-B*1502 and risk of Stevens-Johnson syndrome and toxic epidermal necrolysis: US FDA recommendations. Pharmacogenomics. 2008 Oct;9(10):1543-6. doi: 10.2217/14622416.9.10.1543.
• [14] Common risk allele in aromatic antiepileptic-drug induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Han Chinese. Pharmacogenomics. 2010 Mar;11(3):349-56. doi: 10.2217/pgs.09.162.
• [15] HLA-B*5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol. Proc Natl Acad Sci U S A. 2005 Mar 15;102(11):4134-9. doi: 10.1073/pnas.0409500102. Epub 2005 Mar 2.
• [16] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [17] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [18] HLA-B alleles associated with severe cutaneous reactions to antiepileptic drugs in Han Chinese. Epilepsia. 2013 Jul;54(7):1307-14. doi: 10.1111/epi.12217. Epub 2013 May 20.
• [19] Genetic variations in HLA-B region and hypersensitivity reactions to abacavir. Lancet. 2002 Mar 30;359(9312):1121-2. doi: 10.1016/S0140-6736(02)08158-8.
• [20] HLA-B*5701 genotype is a major determinant of drug-induced liver injury due to flucloxacillin. Nat Genet. 2009 Jul;41(7):816-9. doi: 10.1038/ng.379. Epub 2009 May 31.
• [21] HLA alleles influence the clinical signature of amoxicillin-clavulanate hepatotoxicity. PLoS One. 2013 Jul 9;8(7):e68111. doi: 10.1371/journal.pone.0068111. Print 2013.
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