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

General Information of Drug (ID: DMIHRNA)

• Drug Name: Tolazamide Drug Info
• Synonyms: Diabewas; Norglycin; Tolamide; Tolanase; Tolazamida; Tolazamidum; Tolazolamide; Tolinase; Pharmacia Brand of Tolazamide; T 2408; U 17835; Tolazamida [INN-Spanish]; Tolazamidum [INN-Latin]; Tolinase (TN); U-17835; Tolazamide (JP15/USP/INN); Tolazamide [USAN:INN:BAN:JAN]; N-(p-Toluenesulfonyl)-N'-hexamethyleniminourea; N-[(azepan-1-ylamino)carbonyl]-4-methylbenzenesulfonamide; N-(((hexahydro-1H-azepin-1-yl)amino)carbonyl)-4-methylbenzenesulfonamide; Benzenesulfonamide, {N-[[(hexahydro-1H-azepin-1-yl)amino]carbonyl]-4-methyl-}; N-(((Hexahydro-1H-azepin-1-yl)-amino)carbonyl)-4-methylbenzenesulfonamide; 1-(((((4-Methylphenyl)sulfonyl)amino)carbonyl)amino)azepane; 1-(Hexahydro-1-azepinyl)-3-p-tolylsulfonylurea; 1-(Hexahydro-1H-azepin-1-yl)-3-(p-toluenesulfonyl)urea; 1-(Hexahydro-1H-azepin-1-yl)-3-(p-tolylsulfonyl)urea; 1-(azepan-1-yl)-3-(4-methylphenyl)sulfonylurea; 3-azepan-1-yl-1-(4-methylphenyl)sulfonyl-urea; 4-(p-Tolylsulfonyl)-1,1-hexamethylene; 4-(p-Tolylsulfonyl)-1,1-hexamethylenesemicarbazide; 59866P

Indication

Disease Entry	ICD 11	Status	REF
Diabetic complication	5A2Y	Approved	[1]

• Therapeutic Class: Hypoglycemic Agents
• Cross-matching ID:
  PubChem CID: 5503
  ChEBI ID: CHEMBL817
  CAS Number: CAS 1156-19-0
  TTD Drug ID: DMIHRNA
  INTEDE Drug ID: DR1611
  ACDINA Drug ID: D00684

Molecule-Related Drug Atlas

Drug(s) Targeting Inward rectifier potassium channel Kir1.2 (KCNJ10)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Glipizide	DMZA5PQ	Diabetic complication	5A2Y	Approved	[4]
Chlorpropamide	DMPHZQE	Non-insulin dependent diabetes	5A11	Approved	[5]
Glisoxepide	DMJPR2B	Non-insulin dependent diabetes	5A11	Approved	[6]
Gliquidone	DMB0EUX	Diabetic complication	5A2Y	Approved	[7]
Mitiglinide	DMP8HEL	Diabetic complication	5A2Y	Approved	[8]
Glycodiazine	DM1WL9O	Diabetic complication	5A2Y	Approved	[9]
Sulfonylthioureas	DMBG0H1	Discovery agent	N.A.	Investigative	[10]

Drug(s) Metabolized By Cytochrome P450 2C9 (CYP2C9)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[11]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[12]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[13]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[14]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[15]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[14]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[16]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[17]
Estrone	DM5T6US	Acne vulgaris	ED80	Approved	[18]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[19]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Inward rectifier potassium channel Kir1.2 (KCNJ10)	TTG140O	KCJ10_HUMAN	Blocker	[2]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 2C9 (CYP2C9) Main DME	DE5IED8	CP2C9_HUMAN	Substrate	[3]

References

• [1] 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: 6847).
• [2] Inhibition of ATP-activated potassium channels exerts pressor effects and improves survival in a rat model of severe hemorrhagic shock. Shock. 1996 Jun;5(6):391-4.
• [3] Clinically and pharmacologically relevant interactions of antidiabetic drugs. Ther Adv Endocrinol Metab. 2016 Apr;7(2):69-83.
• [4] Triggering and amplification of insulin secretion by dimethyl alpha-ketoglutarate, a membrane permeable alpha-ketoglutarate analogue. Eur J Pharmacol. 2009 Apr 1;607(1-3):41-6.
• [5] Effect of the chlorpropamide and fructose-1,6-bisphosphate of soluble TNF receptor II levels. Pharmacol Res. 2004 May;49(5):449-53.
• [6] Bepridil, an antiarrhythmic drug, opens mitochondrial KATP channels, blocks sarcolemmal KATP channels, and confers cardioprotection. J Pharmacol Exp Ther. 2006 Jan;316(1):182-8.
• [7] Hydroxyl-substituted sulfonylureas as potent inhibitors of specific [3H]glyburide binding to rat brain synaptosomes. Bioorg Med Chem. 2003 May 1;11(9):2099-113.
• [8] Carboxyl-glucuronidation of mitiglinide by human UDP-glucuronosyltransferases. Biochem Pharmacol. 2007 Jun 1;73(11):1842-51.
• [9] Coupling between proximal tubular transport processes. Studies with ouabain, SITS and HCO3-free solutions. Pflugers Arch. 1977 Apr 25;368(3):245-52.
• [10] Cardioselective K(ATP) channel blockers derived from a new series of m-anisamidoethylbenzenesulfonylthioureas. J Med Chem. 2001 Mar 29;44(7):1085-98.
• [11] Progesterone and testosterone hydroxylation by cytochromes P450 2C19, 2C9, and 3A4 in human liver microsomes. Arch Biochem Biophys. 1997 Oct 1;346(1):161-9.
• [12] Tamoxifen inhibits cytochrome P450 2C9 activity in breast cancer patients. J Chemother. 2006 Aug;18(4):421-4.
• [13] Characterization of the oxidative metabolites of 17beta-estradiol and estrone formed by 15 selectively expressed human cytochrome p450 isoforms. Endocrinology. 2003 Aug;144(8):3382-98.
• [14] Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
• [15] Drug-drug interactions with imatinib: an observational study. Medicine (Baltimore). 2016 Oct;95(40):e5076.
• [16] Drug interactions with calcium channel blockers: possible involvement of metabolite-intermediate complexation with CYP3A. Drug Metab Dispos. 2000 Feb;28(2):125-30.
• [17] New insights into the structural features and functional relevance of human cytochrome P450 2C9. Part I. Curr Drug Metab. 2009 Dec;10(10):1075-126.
• [18] A potential role for the estrogen-metabolizing cytochrome P450 enzymes in human breast carcinogenesis. Breast Cancer Res Treat. 2003 Dec;82(3):191-7.
• [19] A mechanistic approach to antiepileptic drug interactions. Ann Pharmacother. 1998 May;32(5):554-63.