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

General Information of Drug (ID: DM8J0MK)

• Drug Name: GEA-6414 Drug Info
• Synonyms: Tolfenamic acid; Acide tolfenamique; Acido tolfenamico; Acidum tolfenamicum; Bifenac; Clotam; GEA 6414; Tolfedine; tolfenamic acid; 13710-19-5; 2-(3-Chloro-2-methylanilino)benzoic acid; 2-[(3-Chloro-2-methylphenyl)amino]benzoic Acid; 3G943U18KM; Anthranilic acid, N-(3-chloro-o-tolyl)-; Benzoic acid, 2-[(3-chloro-2-methylphenyl)amino]-; CAS-13710-19-5; CHEBI:32243; N-(2-Methyl-3-chlorophenyl)anthranilic acid; N-(3-Chloro-2-methylphenyl)anthranilic acid; N-(3-Chloro-o-tolyl)-anthranilic acid; NCGC00016705-05; UNII-3G943U18KM
• Cross-matching ID:
  PubChem CID: 610479
  ChEBI ID: CHEMBL121626
  CAS Number: CAS 13710-19-5
  TTD Drug ID: DM8J0MK
  INTEDE Drug ID: DR1613

Molecule-Related Drug Atlas

Drug(s) Metabolized By Cytochrome P450 3A4 (CYP3A4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[5]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[6]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[7]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[8]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[9]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[10]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[11]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[12]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[6]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[13]

Drug(s) Metabolized By Cytochrome P450 102A1 (cyp102)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[14]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[2]
Propranolol	DM79NTF	Angina pectoris	BA40	Approved	[15]
Dextromethorphan	DMUDJZM	Allergic rhinitis	CA08.0	Approved	[14]
Nifedipine	DMSVOZT	Angina pectoris	BA40	Approved	[16]
Chlorzoxazone	DMCYVDT	Acute pain	MG31	Approved	[16]
Amodiaquine	DME4RA8	Malaria	1F40-1F45	Approved	[14]
Buspirone	DMBS632	Anxiety disorder	6B00-6B0Z	Approved	[14]
Mefenamic acid	DMK7HFI	Dysmenorrhea	GA34.3	Approved	[2]
Meclofenamic acid	DM05FXR	Ankylosing spondylitis	FA92.0	Approved	[2]

Drug(s) Affected By Proteasome subunit beta type-9 (PSMB9)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Salicyclic acid	DM2F8XZ	Acne vulgaris	ED80	Approved	[4]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[17]
Calcitriol	DM8ZVJ7	Congenital alopecia	LC30	Approved	[18]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[19]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[20]
Ivermectin	DMDBX5F	Intestinal strongyloidiasis due to nematode parasite	1F6B	Approved	[21]
Sodium lauryl sulfate	DMLJ634	Constipation	DD91.1	Approved	[22]
Dexamethasone	DMMWZET	Acute adrenal insufficiency		Approved	[23]
Azathioprine	DMMZSXQ	Lupus nephritis	4A40.0Y	Approved	[24]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[4]

Drug(s) Affected By Proteasome subunit beta type-10 (PSMB10)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Selenium	DM25CGV	N. A.	N. A.	Approved	[25]
Salicyclic acid	DM2F8XZ	Acne vulgaris	ED80	Approved	[4]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[26]
Testosterone	DM7HUNW	Hot flushes	GA30	Approved	[27]
Calcitriol	DM8ZVJ7	Congenital alopecia	LC30	Approved	[27]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[28]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[29]
Temozolomide	DMKECZD	Adenocarcinoma	2D40	Approved	[30]
Sodium lauryl sulfate	DMLJ634	Constipation	DD91.1	Approved	[22]
Cupric Sulfate	DMP0NFQ	Fungal infection	1F29-1F2F	Approved	[31]

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	[32]
Meclofenamic acid	DM05FXR	Ankylosing spondylitis	FA92.0	Approved	[33]
Diazepam	DM08E9O	Alcohol withdrawal		Approved	[34]
Levonorgestrel	DM1DP7T	Atypical endometrial hyperplasia		Approved	[35]
Desogestrel	DM27U4Y	Contraception	QA21	Approved	[35]
Salicyclic acid	DM2F8XZ	Acne vulgaris	ED80	Approved	[33]
Sulindac	DM2QHZU	Acute myelogenous leukaemia	2A41	Approved	[33]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[36]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[37]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[38]

Molecular Interaction Atlas of This Drug

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[1]
Cytochrome P450 102A1 (cyp102)	DE4OGUF	CPXB_BACMB	Substrate	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Aldo-keto reductase family 1 member C3 (AKR1C3)	OTU2SXBA	AK1C3_HUMAN	Gene/Protein Processing	[3]
Proteasome subunit beta type-10 (PSMB10)	OTURUR9B	PSB10_HUMAN	Gene/Protein Processing	[4]
Proteasome subunit beta type-9 (PSMB9)	OTFV57T8	PSB9_HUMAN	Gene/Protein Processing	[4]

References

• [1] Integrated analysis on the physicochemical properties of dihydropyridine calcium channel blockers in grapefruit juice interactions. Curr Pharm Biotechnol. 2012 Jul;13(9):1705-17.
• [2] Both reactivity and accessibility are important in cytochrome P450 metabolism: a combined DFT and MD study of fenamic acids in BM3 mutants. J Chem Inf Model. 2019 Feb 25;59(2):743-753.
• [3] Roles of rat and human aldo-keto reductases in metabolism of farnesol and geranylgeraniol. Chem Biol Interact. 2011 May 30;191(1-3):261-8. doi: 10.1016/j.cbi.2010.12.017. Epub 2010 Dec 25.
• [4] Pathophysiological roles of aldo-keto reductases (AKR1C1 and AKR1C3) in development of cisplatin resistance in human colon cancers. Chem Biol Interact. 2013 Feb 25;202(1-3):234-42.
• [5] Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
• [6] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [7] Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
• [8] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [9] Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
• [10] Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
• [11] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [12] The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
• [13] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
• [14] The bacterial P450 BM3: a prototype for a biocatalyst with human P450 activities. Trends Biotechnol. 2007 Jul;25(7):289-98.
• [15] acillus megaterium SF185 spores exert protective effects against oxidative stress in vivo and in vitro. Sci Rep. 2019 Aug 19;9(1):12082.
• [16] Wild-type CYP102A1 as a biocatalyst: turnover of drugs usually metabolised by human liver enzymes. J Biol Inorg Chem. 2007 Mar;12(3):313-23.
• [17] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [18] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [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] Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development. PLoS One. 2013;8(3):e58822.
• [21] 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.
• [22] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [23] Inhibition of PARP1 Increases IRF-dependent Gene Transcription in Jurkat Cells. Curr Med Sci. 2019 Jun;39(3):356-362. doi: 10.1007/s11596-019-2043-1. Epub 2019 Jun 17.
• [24] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [25] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [26] Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
• [27] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [28] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [29] 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.
• [30] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [31] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [32] 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.
• [33] 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.
• [34] 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.
• [35] Progestins as inhibitors of the human 20-ketosteroid reductases, AKR1C1 and AKR1C3. Chem Biol Interact. 2011 May 30;191(1-3):227-33.
• [36] 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.
• [37] AKR1C3 as a potential target for the inhibitory effect of dietary flavonoids. Chem Biol Interact. 2009 Mar 16;178(1-3):138-44.
• [38] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.