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

General Information of Drug (ID: DMR6N7H)

• Drug Name: Acetohexamide Drug Info
• Synonyms: Acetohexamid; Acetohexamida; Acetohexamidum; Dimelin; Dimelor; Dymelor; Gamadiabet; Hypoglicil; Metaglucina; Minoral; Ordimel; Tsiklamid; Acetohexamide Lilly Brand; Acetohexamide Salvat Brand; Lilly Brand of Acetohexamide; Ord imel; Salvat Brand of Acetohexamide; U 14812; A-178; Acetohexamida [INN-Spanish]; Acetohexamidum [INN-Latin]; Dimelin (antidiabetic); Dymelor (TN); U-14812; Acetohexamide (JP15/USP/INN); Acetohexamide [USAN:INN:BAN:JAN]; N-(p-Acetylbenzenesulfonyl)-N'-cyclohexylurea; N-(p-Acetylphenylsulfonyl)-N'-cyclohexylurea; 1-((p-Acetylphenyl)sulfonyl)-3-cyclohexylurea; 1-(4-acetylphenyl)sulfonyl-3-cyclohexylurea; 1-(p-Acetylbenzenesulfonyl)-3-cyclohexylurea; 3-cyclohexyl-1-(p-acetylphenylsulfonyl)urea; 4-Acetyl-N-((cyclohexylamino)carbonyl)benzenesulfonamide; 4-Acetyl-N-[(cyclohexylamino)-carbonyl]benzenesulfonamide; 4-Acetyl-N-[(cyclohexylamino)carbonyl]benzenesulfonamide; 4-acetyl-N-((cyclohexylamino)carbonyl)benzenesulf onamide

Indication

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

• Therapeutic Class: Hypoglycemic Agents
• Cross-matching ID:
  PubChem CID: 1989
  ChEBI ID: CHEBI:28052
  CAS Number: CAS 968-81-0
  TTD Drug ID: DMR6N7H
  VARIDT Drug ID: DR01113
  INTEDE Drug ID: DR0039

Molecule-Related Drug Atlas

Drug(s) Targeting ATP-binding cassette transporter C8 (ABCC8)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Glibenclamide	DM8JXPZ	Diabetic complication	5A2Y	Approved	[7]
Tolbutamide	DM02AWV	Advanced cancer	2A00-2F9Z	Approved	[8]
Repaglinide	DM5SXUV	Diabetic complication	5A2Y	Approved	[9]
Glimepiride	DM5FSJA	Diabetic complication	5A2Y	Approved	[10]
Gliclazide	DMN6QO5	Diabetic complication	5A2Y	Approved	[11]
NN-414	DMRJEXM	Type-1 diabetes	5A10	Phase 1	[12]
HBR-985	DMKDBFL	Discovery agent	N.A.	Investigative	[13]
NS-11757	DM98VMZ	Atrial fibrillation	BC81.3	Investigative	[14]

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[15]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[16]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[17]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[18]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[19]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[18]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[20]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[21]
Estrone	DM5T6US	Acne vulgaris	ED80	Approved	[22]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[23]

Drug(s) Affected By Albumin (ALB)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[24]
Sulfamethoxazole	DMB08GE	Acute otitis media	AB00	Approved	[6]
Tolbutamide	DM02AWV	Advanced cancer	2A00-2F9Z	Approved	[25]
Diazepam	DM08E9O	Alcohol withdrawal		Approved	[26]
Sertraline	DM0FB1J	Coronary heart disease	BA80.Z	Approved	[27]
Methimazole	DM25FL8	Hyperthyroidism	5A02	Approved	[28]
Imipramine	DM2NUH3	Depression	6A70-6A7Z	Approved	[29]
Colchicine	DM2POTE	Acute gout flare	FA25.0	Approved	[30]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[31]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[32]

Drug(s) Affected By Carbonyl reductase 3 (CBR3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Daunorubicin	DMQUSBT	Acute monocytic leukemia		Approved	[33]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[34]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[35]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[36]
Ivermectin	DMDBX5F	Intestinal strongyloidiasis due to nematode parasite	1F6B	Approved	[37]
Bortezomib	DMNO38U	Leukemia		Approved	[38]
Cupric Sulfate	DMP0NFQ	Fungal infection	1F29-1F2F	Approved	[39]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[24]
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[33]
Oxcarbazepine	DM5PU6O	Epilepsy	8A60-8A68	Approved	[40]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
ATP-binding cassette transporter C8 (ABCC8)	TTP835K	ABCC8_HUMAN	Modulator	[2]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Substrate	[3]
Short-chain dehydrogenase/reductase retSDR1 (DHRS3)	DEXPVUN	DHRS3_HUMAN	Substrate	[4]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Protein Interaction/Cellular Processes	[5]
Carbonyl reductase 3 (CBR3)	OT9G6SF0	CBR3_HUMAN	Drug Response	[6]

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: 6793).
• [2] Diabetes and insulin secretion: the ATP-sensitive K+ channel (K ATP) connection.Diabetes.2005 Nov;54(11):3065-72.
• [3] Clinically and pharmacologically relevant interactions of antidiabetic drugs. Ther Adv Endocrinol Metab. 2016 Apr;7(2):69-83.
• [4] Molecular and biochemical characterisation of human short-chain dehydrogenase/reductase member 3 (DHRS3). Chem Biol Interact. 2015 Jun 5;234:178-87.
• [5] Characterization of the binding of sulfonylurea drugs to HSA by high-performance affinity chromatography. J Chromatogr B Analyt Technol Biomed Life Sci. 2010 Jun 1;878(19):1590-8. doi: 10.1016/j.jchromb.2010.04.019.
• [6] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [7] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [8] Expression of an activating mutation in the gene encoding the KATP channel subunit Kir6.2 in mouse pancreatic beta cells recapitulates neonatal diabetes. J Clin Invest. 2009 Jan;119(1):80-90.
• [9] Metformin/Repaglinide (PrandiMet) for type 2 diabetes. Med Lett Drugs Ther. 2009 Jun 1;51(1313):41-3.
• [10] Mechanism of disopyramide-induced hypoglycaemia in a patient with Type 2 diabetes. Diabet Med. 2009 Jan;26(1):76-8.
• [11] Structural basis for the interference between nicorandil and sulfonylurea action. Diabetes. 2001 Oct;50(10):2253-9.
• [12] Attenuation of hyperinsulinemia by NN414, a SUR1/Kir6.2 selective K-adenosine triphosphate channel opener, improves glucose tolerance and lipid profile in obese Zucker rats.Metabolism.2004 Apr;53(4):441-7.
• [13] Cardioselective K(ATP) channel blockers derived from a new series of m-anisamidoethylbenzenesulfonylthioureas. J Med Chem. 2001 Mar 29;44(7):1085-98.
• [14] 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: 2944).
• [15] 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.
• [16] Tamoxifen inhibits cytochrome P450 2C9 activity in breast cancer patients. J Chemother. 2006 Aug;18(4):421-4.
• [17] 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.
• [18] Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
• [19] Drug-drug interactions with imatinib: an observational study. Medicine (Baltimore). 2016 Oct;95(40):e5076.
• [20] Drug interactions with calcium channel blockers: possible involvement of metabolite-intermediate complexation with CYP3A. Drug Metab Dispos. 2000 Feb;28(2):125-30.
• [21] 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.
• [22] A potential role for the estrogen-metabolizing cytochrome P450 enzymes in human breast carcinogenesis. Breast Cancer Res Treat. 2003 Dec;82(3):191-7.
• [23] A mechanistic approach to antiepileptic drug interactions. Ann Pharmacother. 1998 May;32(5):554-63.
• [24] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [25] A protein-coated magnetic beads as a tool for the rapid drug-protein binding study. J Pharm Biomed Anal. 2010 Jul 8;52(3):420-4. doi: 10.1016/j.jpba.2009.06.023. Epub 2009 Jun 18.
• [26] The three recombinant domains of human serum albumin. Structural characterization and ligand binding properties. J Biol Chem. 1999 Oct 8;274(41):29303-10. doi: 10.1074/jbc.274.41.29303.
• [27] Exploring binding properties of sertraline with human serum albumin: Combination of spectroscopic and molecular modeling studies. Chem Biol Interact. 2015 Dec 5;242:235-46. doi: 10.1016/j.cbi.2015.10.006. Epub 2015 Oct 22.
• [28] Low-expressional IGF1 mediated methimazole-induced liver developmental toxicity in fetal mice. Toxicology. 2018 Sep 1;408:70-79. doi: 10.1016/j.tox.2018.07.004. Epub 2018 Jul 7.
• [29] Use of peak decay analysis and affinity microcolumns containing silica monoliths for rapid determination of drug-protein dissociation rates. J Chromatogr A. 2011 Apr 15;1218(15):2072-8. doi: 10.1016/j.chroma.2010.09.070. Epub 2010 Oct 16.
• [30] [Colchicine in chronic liver disease of alcoholic etiology. Double-blind, randomized study of its effects on blood levels of plasma proteins and clinical course in patients]. Rev Assoc Med Bras (1992). 1995 May-Jun;41(3):207-12.
• [31] Editor's Highlight: Modeling Compound-Induced Fibrogenesis In Vitro Using Three-Dimensional Bioprinted Human Liver Tissues. Toxicol Sci. 2016 Dec;154(2):354-367. doi: 10.1093/toxsci/kfw169. Epub 2016 Sep 7.
• [32] Covalent binding of the flavonoid quercetin to human serum albumin. J Agric Food Chem. 2005 May 18;53(10):4194-7. doi: 10.1021/jf050061m.
• [33] Naturally occurring variants of human CBR3 alter anthracycline in vitro metabolism. J Pharmacol Exp Ther. 2010 Mar;332(3):755-63.
• [34] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [35] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [36] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [37] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [38] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [39] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [40] The role of carbonyl reducing enzymes in oxcarbazepine in vitro metabolism in man. Chem Biol Interact. 2014 Sep 5;220:241-7.