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

General Information of Drug (ID: DM9SX6Y)

Drug Name

INDISULAM Drug Info

Synonyms

Indisulam; 165668-41-7; E7070; N-(3-chloro-1H-indol-7-yl)benzene-1,4-disulfonamide; UNII-WJ98J3NM90; E-7070; E 7070; N-(3-Chloro-1H-indol-7-yl)-1,4-benzenedisulfonamide; CHEMBL77517; WJ98J3NM90; N1-(3-chloro-1H-indol-7-yl)benzene-1,4-disulfonamide; 1,4-Benzenedisulfonamide, N-(3-chloro-1H-indol-7-yl)-; ER-35744; N-(3-Chloro-1H-indol-7-yl)benzene-1,4disulfonamide; Indisulam (IND); indisulam (e7070); Indisulam (USAN/INN); AC1Q6VCX; AC1L50QL; SCHEMBL91389; N-(3-chloro-7-indolyl)-1,4-benzenedisulphonamide; Indisulam [USAN:INN:BAN]

Indication

Disease Entry	ICD 11	Status	REF
Lymphoma	2A80-2A86	Phase 2	[1]

Cross-matching ID

PubChem CID: 216468
ChEBI ID: CHEBI:145431
CAS Number: CAS 165668-41-7
TTD Drug ID: DM9SX6Y
INTEDE Drug ID: DR0873

Molecule-Related Drug Atlas

Molecule Type:

DTT

DME

DOT

Drug Status:

Clinical Trial Drug(s)

Patented Agent(s)

Approved Drug(s)

Download the Complete Related Drug List

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	[6]
PARABEN	DMEW5Z8	N. A.	N. A.	Phase 3	[7]
PHENOL	DM1QSM3	N. A.	N. A.	Phase 2/3	[6]
Coumate	DMVKW0N	Breast cancer	2C60-2C65	Phase 2	[8]
Girentuximab I-124	DMG3O2Z	Renal cell carcinoma	2C90	Phase 2	[9]
SULFAMIDE	DMMAS3K	N. A.	N. A.	Phase 1	[10]
BAY 79-4620	DM14XQN	Solid tumour/cancer	2A00-2F9Z	Phase 1	[11]
90Y-cG250	DMJR6TC	Solid tumour/cancer	2A00-2F9Z	Phase 1	[12]
FERULIC ACID	DMJC7NF	Discovery agent	N.A.	Patented	[7]
PMID30074415-Compound-GS3	DM2G8DN	N. A.	N. A.	Patented	[13]
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Drug(s) Metabolized By Cytochrome P450 2C9 (CYP2C9)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[14]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[15]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[16]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[17]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[18]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[17]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[19]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[20]
Estrone	DM5T6US	Acne vulgaris	ED80	Approved	[21]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[22]
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Drug(s) Metabolized By Mephenytoin 4-hydroxylase (CYP2C19)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Amoxicillin	DMUYNEI	Acute otitis media	AB00	Approved	[23]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[14]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[24]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[25]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[17]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[26]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[27]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[22]
Quinine	DMSWYF5	Malaria	1F40-1F45	Approved	[28]
Propofol	DMB4OLE	Anaesthesia	9A78.6	Approved	[29]
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Drug(s) Affected By Retinoblastoma-associated protein (RB1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Indomethacin	DMSC4A7	Bursitis		Approved	[30]
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[31]
Gefitinib	DM15F0X	Colon adenocarcinoma		Approved	[32]
Talazoparib	DM1KS78	Breast cancer	2C60-2C65	Approved	[33]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[34]
Trametinib	DM2JGQ3	Melanoma	2C30	Approved	[35]
Sulindac	DM2QHZU	Acute myelogenous leukaemia	2A41	Approved	[36]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[37]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[38]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[39]
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Molecular Interaction Atlas of This Drug

Molecular Interaction Atlas

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Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Carbonic anhydrase IX (CA-IX)	TT2LVK8	CAH9_HUMAN	Modulator	[2]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Substrate	[3]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Substrate	[4]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Retinoblastoma-associated protein (RB1)	OTQJUJMZ	RB_HUMAN	Post-Translational Modifications	[5]

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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: 7046).
2	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.
3	PK/PD model of indisulam and capecitabine: interaction causes excessive myelosuppression. Clin Pharmacol Ther. 2008 Jun;83(6):829-39.
4	CYP2C9 and CYP2C19 polymorphic forms are related to increased indisulam exposure and higher risk of severe hematologic toxicity. Clin Cancer Res. 2007 May 15;13(10):2970-6.
5	A phase II clinical and pharmacodynamic study of E7070 in patients with metastatic, recurrent, or refractory squamous cell carcinoma of the head and neck: modulation of retinoblastoma protein phosphorylation by a novel chloroindolyl sulfonamide cell cycle inhibitor. Clin Cancer Res. 2004 Jul 15;10(14):4680-7. doi: 10.1158/1078-0432.CCR-04-0229.
6	Carbonic anhydrase inhibitors. Antioxidant polyphenols effectively inhibit mammalian isoforms I-XV. Bioorg Med Chem Lett. 2010 Sep 1;20(17):5050-3.
7	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.
8	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.
9	Potential role of (124)I-girentuximab in the presurgical diagnosis of clear-cell renal cell cancer. Biologics. 2012;6:395-407.
10	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.
11	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.
12	Application of monoclonal antibody G250 recognizing carbonic anhydrase IX in renal cell carcinoma. Int J Mol Sci. 2013 May 29;14(6):11402-23.
13	Carbonic anhydrase inhibitors as antitumor/antimetastatic agents: a patent review (2008-2018).Expert Opin Ther Pat. 2018 Oct;28(10):729-740.
14	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.
15	Tamoxifen inhibits cytochrome P450 2C9 activity in breast cancer patients. J Chemother. 2006 Aug;18(4):421-4.
16	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.
17	Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
18	Drug-drug interactions with imatinib: an observational study. Medicine (Baltimore). 2016 Oct;95(40):e5076.
19	Drug interactions with calcium channel blockers: possible involvement of metabolite-intermediate complexation with CYP3A. Drug Metab Dispos. 2000 Feb;28(2):125-30.
20	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.
21	A potential role for the estrogen-metabolizing cytochrome P450 enzymes in human breast carcinogenesis. Breast Cancer Res Treat. 2003 Dec;82(3):191-7.
22	A mechanistic approach to antiepileptic drug interactions. Ann Pharmacother. 1998 May;32(5):554-63.
23	High-dose rabeprazole/amoxicillin therapy as the second-line regimen after failure to eradicate H. pylori by triple therapy with the usual doses of a proton pump inhibitor, clarithromycin and amoxicillin. Hepatogastroenterology. 2003 Nov-Dec;50(54):2274-8.
24	Cytochrome P450 pharmacogenetics and cancer. Oncogene. 2006 Mar 13;25(11):1679-91.
25	CYP2C19*17 is associated with decreased breast cancer risk. Breast Cancer Res Treat. 2009 May;115(2):391-6.
26	Cytochromes of the P450 2C subfamily are the major enzymes involved in the O-demethylation of verapamil in humans. Naunyn Schmiedebergs Arch Pharmacol. 1995 Dec;353(1):116-21.
27	Diclofenac and its derivatives as tools for studying human cytochromes P450 active sites: particular efficiency and regioselectivity of P450 2Cs. Biochemistry. 1999 Oct 26;38(43):14264-70.
28	Organic anion-transporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver. Gastroenterology. 2001 Feb;120(2):525-33.
29	Possible involvement of multiple human cytochrome P450 isoforms in the liver metabolism of propofol. Br J Anaesth. 1998 Jun;80(6):788-95.
30	Indomethacin inhibits cell growth of medullary thyroid carcinoma by reducing cell cycle progression into S phase. Exp Biol Med (Maywood). 2008 Nov;233(11):1433-40. doi: 10.3181/0804-RM-127. Epub 2008 Sep 12.
31	Therapeutically activating RB: reestablishing cell cycle control in endocrine therapy-resistant breast cancer. Endocr Relat Cancer. 2011 Apr 28;18(3):333-45. doi: 10.1530/ERC-10-0262. Print 2011 Jun.
32	Effects and mechanisms of betulinic acid on improving EGFR TKI-resistance of lung cancer cells. Environ Toxicol. 2018 Nov;33(11):1153-1159.
33	BMN 673 (talazoparib): A potent PARP inhibitor for triple negative breast cancer with different genetic profile. J Biochem Mol Toxicol. 2019 May;33(5):e22286. doi: 10.1002/jbt.22286. Epub 2019 Jan 23.
34	Microarray analysis of H2O2-, HNE-, or tBH-treated ARPE-19 cells. Free Radic Biol Med. 2002 Nov 15;33(10):1419-32.
35	Combination small molecule MEK and PI3K inhibition enhances uveal melanoma cell death in a mutant GNAQ- and GNA11-dependent manner. Clin Cancer Res. 2012 Aug 15;18(16):4345-55. doi: 10.1158/1078-0432.CCR-11-3227. Epub 2012 Jun 25.
36	Sulindac induces specific degradation of the HPV oncoprotein E7 and causes growth arrest and apoptosis in cervical carcinoma cells. Cancer Lett. 2007 Jan 8;245(1-2):103-11. doi: 10.1016/j.canlet.2005.12.034. Epub 2006 Feb 20.
37	Melanoma coordinates general and cell-specific mechanisms to promote methotrexate resistance. Exp Cell Res. 2012 Jun 10;318(10):1146-59.
38	HMG-CoA reductase inhibitor simvastatin inhibits cell cycle progression at the G1/S checkpoint in immortalized lymphocytes from Alzheimer's disease patients independently of cholesterol-lowering effects. J Pharmacol Exp Ther. 2008 Jan;324(1):352-9. doi: 10.1124/jpet.107.128959. Epub 2007 Oct 10.
39	Inhibition of prostate cancer cell colony formation by the flavonoid quercetin correlates with modulation of specific regulatory genes. Clin Diagn Lab Immunol. 2004 Jan;11(1):63-9. doi: 10.1128/cdli.11.1.63-69.2004.