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

General Information of Drug (ID: DMTMNO7)

• Drug Name: 7-hydroxycoumarin Drug Info
• Synonyms: Umbelliferone; 93-35-6; 7-Hydroxy-2H-chromen-2-one; Skimmetin; Hydrangin; 7-hydroxycoumarine; 7-Oxycoumarin; Umbelliferon; Skimmetine; Hydrangine; 2H-1-Benzopyran-2-one, 7-hydroxy-; 7-Hydroxy-2H-1-benzopyran-2-one; Coumarin, 7-hydroxy-; beta-Umbelliferone; 7-hydroxychromen-2-one; 7 HC; UNII-60Z60NTL4G; 7-hydroxy-coumarin; NSC 19790; CCRIS 3591; NSC19790; EINECS 202-240-3; 7H-1-Benzopyran-7-one, 2-hydroxy-; BRN 0127683; CHEMBL51628; AI3-38054; 7-hydroxy-1-benzopyran-2-one; 7-HC; 60Z60NTL4G; CHEBI:27510; UMBELLIFERONE

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 5281426
  ChEBI ID: CHEMBL51628
  CAS Number: CAS 93-35-6
  TTD Drug ID: DMTMNO7

Molecule-Related Drug Atlas

Drug(s) Targeting G1/S-specific cyclin-D1 (CCND1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ABT-263	DMNE56X	Myelofibrosis	2A20.2	Phase 3	[6]
Briciclib	DMK7BND	Solid tumour/cancer	2A00-2F9Z	Phase 1	[7]
4-[(3,5-diamino-1H-pyrazol-4-yl)diazenyl]phenol	DMSKJ1X	Discovery agent	N.A.	Investigative	[8]
3,4-di-(4-methoxyphenyl)-1H-pyrrole-2,5-dione	DMDO175	Discovery agent	N.A.	Investigative	[9]
3,4-diphenyl-1H-pyrrole-2,5-dione	DMPK6YT	Discovery agent	N.A.	Investigative	[9]
3-(4-methoxyphenyl)-4-phenyl-1H-pyrrole-2,5-dione	DMGC7RY	Discovery agent	N.A.	Investigative	[9]
3-(indole-3-yl)-4-phenyl-1H-pyrrole-2,5-dione	DM3EV9N	Discovery agent	N.A.	Investigative	[9]

Drug(s) Targeting Carbonic anhydrase IX (CA-IX)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Curcumin	DMQPH29	Solid tumour/cancer	2A00-2F9Z	Phase 3	[10]
PARABEN	DMEW5Z8	N. A.	N. A.	Phase 3	[11]
PHENOL	DM1QSM3	N. A.	N. A.	Phase 2/3	[10]
Coumate	DMVKW0N	Breast cancer	2C60-2C65	Phase 2	[12]
INDISULAM	DM9SX6Y	Lymphoma	2A80-2A86	Phase 2	[13]
Girentuximab I-124	DMG3O2Z	Renal cell carcinoma	2C90	Phase 2	[14]
SULFAMIDE	DMMAS3K	N. A.	N. A.	Phase 1	[15]
BAY 79-4620	DM14XQN	Solid tumour/cancer	2A00-2F9Z	Phase 1	[16]
90Y-cG250	DMJR6TC	Solid tumour/cancer	2A00-2F9Z	Phase 1	[17]
FERULIC ACID	DMJC7NF	Discovery agent	N.A.	Patented	[11]

Drug(s) Affected By Aflatoxin B1 aldehyde reductase member 2 (AKR7A2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[18]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[19]
Ivermectin	DMDBX5F	Intestinal strongyloidiasis due to nematode parasite	1F6B	Approved	[20]
Cupric Sulfate	DMP0NFQ	Fungal infection	1F29-1F2F	Approved	[21]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[22]
Piroxicam	DMTK234	Osteoarthritis	FA00-FA05	Approved	[23]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[24]
Phenobarbital	DMXZOCG	Cluster headache	8A81.0	Approved	[25]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[26]
Menadione	DMSJDTY	Vitamin K deficiency	5B59	Approved	[27]

Drug(s) Affected By Aflatoxin B1 aldehyde reductase member 3 (AKR7A3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Nefazodone	DM4ZS8M	Major depressive disorder	6A70.3	Approved	[28]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[19]
Ethanol	DMDRQZU	Chronic pain	MG30	Approved	[29]
Cupric Sulfate	DMP0NFQ	Fungal infection	1F29-1F2F	Approved	[21]
Chenodiol	DMQ8JIK	Cholelithiasis	DC11	Approved	[30]
Atazanavir	DMSYRBX	Human immunodeficiency virus infection	1C62	Approved	[28]
Benzo(a)pyrene	DMN7J43	N. A.	N. A.	Phase 1	[19]
EMODIN	DMAEDQG	Coronavirus Disease 2019 (COVID-19)	1D6Y	Terminated	[31]
bisphenol A	DM2ZLD7	Discovery agent	N.A.	Investigative	[32]

Drug(s) Affected By Aldo-keto reductase family 1 member C3 (AKR1C3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[33]
Meclofenamic acid	DM05FXR	Ankylosing spondylitis	FA92.0	Approved	[34]
Diazepam	DM08E9O	Alcohol withdrawal		Approved	[35]
Levonorgestrel	DM1DP7T	Atypical endometrial hyperplasia		Approved	[36]
Desogestrel	DM27U4Y	Contraception	QA21	Approved	[36]
Salicyclic acid	DM2F8XZ	Acne vulgaris	ED80	Approved	[34]
Sulindac	DM2QHZU	Acute myelogenous leukaemia	2A41	Approved	[34]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[37]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[38]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[39]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Carbonic anhydrase IX (CA-IX)	TT2LVK8	CAH9_HUMAN	Inhibitor	[2]
G1/S-specific cyclin-D1 (CCND1)	TTFCJ7S	CCND1_HUMAN	Inhibitor	[1]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Aflatoxin B1 aldehyde reductase member 2 (AKR7A2)	OTGEDDM2	ARK72_HUMAN	Gene/Protein Processing	[3]
Aflatoxin B1 aldehyde reductase member 3 (AKR7A3)	OTW3GO4Y	ARK73_HUMAN	Gene/Protein Processing	[3]
Aldo-keto reductase family 1 member C3 (AKR1C3)	OTU2SXBA	AK1C3_HUMAN	Gene/Protein Processing	[3]
UDP-glucuronosyltransferase 1A9	OTPCHAFX	UD19_HUMAN	Biotransformations	[4]
UDP-glucuronosyltransferase 2B15	OTABTFU2	UDB15_HUMAN	Regulation of Drug Effects	[5]

References

• [1] Decrease of cyclin D1 in the human lung adenocarcinoma cell line A-427 by 7-hydroxycoumarin. Lung Cancer. 2001 Nov;34(2):185-94.
• [2] 7,8-disubstituted- but not 6,7-disubstituted coumarins selectively inhibit the transmembrane, tumor-associated carbonic anhydrase isoforms IX and X... Bioorg Med Chem Lett. 2010 Dec 15;20(24):7255-8.
• [3] Hepatoprotective effect of 7-hydroxycoumarin against methyl glyoxal toxicity via activation of Nrf2. Chem Biol Interact. 2017 Oct 1;276:203-209.
• [4] An active and water-soluble truncation mutant of the human UDP-glucuronosyltransferase 1A9. Mol Pharmacol. 2004 Apr;65(4):826-31. doi: 10.1124/mol.65.4.826.
• [5] Stable expression of a human liver UDP-glucuronosyltransferase (UGT2B15) with activity toward steroid and xenobiotic substrates. Drug Metab Dispos. 1994 Sep-Oct;22(5):799-805.
• [6] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [7] Clinical pipeline report, company report or official report of Onconova.
• [8] 4-arylazo-3,5-diamino-1H-pyrazole CDK inhibitors: SAR study, crystal structure in complex with CDK2, selectivity, and cellular effects. J Med Chem. 2006 Nov 2;49(22):6500-9.
• [9] Design, synthesis, and biological evaluation of 3,4-diarylmaleimides as angiogenesis inhibitors. J Med Chem. 2006 Feb 23;49(4):1271-81.
• [10] Carbonic anhydrase inhibitors. Antioxidant polyphenols effectively inhibit mammalian isoforms I-XV. Bioorg Med Chem Lett. 2010 Sep 1;20(17):5050-3.
• [11] Carbonic anhydrase inhibitors. Inhibition of mammalian isoforms I-XIV with a series of natural product polyphenols and phenolic acids. Bioorg Med Chem. 2010 Mar 15;18(6):2159-2164.
• [12] Carbonic anhydrase inhibitors. Interaction of the antitumor sulfamate EMD 486019 with twelve mammalian carbonic anhydrase isoforms: Kinetic and X-r... Bioorg Med Chem Lett. 2008 Aug 1;18(15):4282-6.
• [13] Carbonic anhydrase inhibitors: E7070, a sulfonamide anticancer agent, potently inhibits cytosolic isozymes I and II, and transmembrane, tumor-assoc... Bioorg Med Chem Lett. 2004 Jan 5;14(1):217-23.
• [14] Potential role of (124)I-girentuximab in the presurgical diagnosis of clear-cell renal cell cancer. Biologics. 2012;6:395-407.
• [15] Carbonic anhydrase inhibitors. Inhibition of isozymes I, II, IV, V, and IX with anions isosteric and isoelectronic with sulfate, nitrate, and carbo... Bioorg Med Chem Lett. 2005 Feb 1;15(3):567-71.
• [16] Therapeutic mechanism and efficacy of the antibody-drug conjugate BAY 79-4620 targeting human carbonic anhydrase 9. Mol Cancer Ther. 2012 Feb;11(2):340-9.
• [17] Application of monoclonal antibody G250 recognizing carbonic anhydrase IX in renal cell carcinoma. Int J Mol Sci. 2013 May 29;14(6):11402-23.
• [18] Insights into the transcriptional regulation of the anthracycline reductase AKR7A2 in human cardiomyocytes. Toxicol Lett. 2019 Jun 1;307:11-16.
• [19] 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.
• [20] 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.
• [21] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [22] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [23] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
• [24] Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
• [25] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [26] Inducible protection of human astrocytoma 1321N1 cells against hydrogen peroxide and aldehyde toxicity by 7-hydroxycoumarin is associated with the upregulation of aldo-keto reductases. Neurotoxicology. 2012 Oct;33(5):1368-74.
• [27] Human aldo-keto reductase AKR7A2 protects against the cytotoxicity and mutagenicity of reactive aldehydes and lowers intracellular reactive oxygen species in hamster V79-4 cells. Chem Biol Interact. 2012 Jan 5;195(1):25-34. doi: 10.1016/j.cbi.2011.09.007. Epub 2011 Oct 5.
• [28] Robustness testing and optimization of an adverse outcome pathway on cholestatic liver injury. Arch Toxicol. 2020 Apr;94(4):1151-1172. doi: 10.1007/s00204-020-02691-9. Epub 2020 Mar 10.
• [29] Effects of acute ethanol treatment on NCCIT cells and NCCIT cell-derived embryoid bodies (EBs). Toxicol In Vitro. 2010 Sep;24(6):1696-704. doi: 10.1016/j.tiv.2010.05.017. Epub 2010 May 26.
• [30] Chenodeoxycholic acid significantly impacts the expression of miRNAs and genes involved in lipid, bile acid and drug metabolism in human hepatocytes. Life Sci. 2016 Jul 1;156:47-56.
• [31] Inhibition of human carbonyl reducing enzymes by plant anthrone and anthraquinone derivatives. Chem Biol Interact. 2022 Feb 25;354:109823. doi: 10.1016/j.cbi.2022.109823. Epub 2022 Jan 21.
• [32] Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.
• [33] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [34] Type 5 17beta-hydroxysteroid dehydrogenase/prostaglandin F synthase (AKR1C3): role in breast cancer and inhibition by non-steroidal anti-inflammatory drug analogs. Chem Biol Interact. 2009 Mar 16;178(1-3):221-7.
• [35] Substrate specificity of human 3(20)alpha-hydroxysteroid dehydrogenase for neurosteroids and its inhibition by benzodiazepines. Biol Pharm Bull. 2002 Apr;25(4):441-5.
• [36] Progestins as inhibitors of the human 20-ketosteroid reductases, AKR1C1 and AKR1C3. Chem Biol Interact. 2011 May 30;191(1-3):227-33.
• [37] In-vivo effects of simvastatin and rosuvastatin on global gene expression in peripheral blood leucocytes in a human inflammation model. Pharmacogenet Genomics. 2008 Feb;18(2):109-20.
• [38] AKR1C3 as a potential target for the inhibitory effect of dietary flavonoids. Chem Biol Interact. 2009 Mar 16;178(1-3):138-44.
• [39] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.