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

General Information of Drug (ID: DM8K5IF)

• Drug Name: E7850 Drug Info
• Synonyms: Irofulven

Indication

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Phase 2	[1]

• Cross-matching ID:
  PubChem CID: 148189
  ChEBI ID: CHEBI:135002
  CAS Number: CAS 158440-71-2
  TTD Drug ID: DM8K5IF

Molecule-Related Drug Atlas

Drug(s) Targeting Serine/threonine-protein kinase Chk2 (RAD53)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PMID27410995-Compound-Figure3j	DMJRZLB	N. A.	N. A.	Patented	[5]
XL844	DMHTG38	Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 1	[6]
PMID22564207C25b	DMBMYKQ	Discovery agent	N.A.	Investigative	[7]
DEBROMOHYMENIALDISINE	DMDLER8	Discovery agent	N.A.	Investigative	[8]
2-(4-Phenoxy-phenyl)-1H-benzoimidazol-5-ylamine	DMSPOAT	Discovery agent	N.A.	Investigative	[9]
PV-1019	DMRI1LF	Solid tumour/cancer	2A00-2F9Z	Investigative	[10]
5-Nitro-2-(4-phenoxy-phenyl)-1H-benzoimidazole	DM26MIC	Discovery agent	N.A.	Investigative	[9]
CCT-241533	DMZXFT9	Solid tumour/cancer	2A00-2F9Z	Investigative	[11]
Chk2 inhibitor II	DMNSPFG	Discovery agent	N.A.	Investigative	[12]

Drug(s) Affected By Glutathione reductase, mitochondrial (GSR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[13]
Ketoprofen	DMRKXPT	Bursitis		Approved	[14]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[15]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[16]
Clavulanate	DM2FGRT	Bacteremia	1A73	Approved	[17]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[18]
obeticholic acid	DM3Q1SM	Primary biliary cholangitis	DB96.1	Approved	[19]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[20]
Acetic Acid, Glacial	DM4SJ5Y	infection in the ear canal	AA0Y	Approved	[21]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[22]

Drug(s) Affected By Chimeric ERCC6-PGBD3 protein (ERCC6)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[23]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[24]
Cupric Sulfate	DMP0NFQ	Fungal infection	1F29-1F2F	Approved	[25]
Decitabine	DMQL8XJ	Acute myelogenous leukaemia	2A41	Approved	[26]
Arsenic	DMTL2Y1	N. A.	N. A.	Approved	[27]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[26]
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[28]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[29]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[30]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[31]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Serine/threonine-protein kinase Chk2 (RAD53)	TT9ABMF	CHK2_HUMAN	Modulator	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Chimeric ERCC6-PGBD3 protein (ERCC6)	OT2QZKSF	ERPG3_HUMAN	Drug Response	[3]
Glutathione reductase, mitochondrial (GSR)	OTM2TUYM	GSHR_HUMAN	Gene/Protein Processing	[4]

References

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• [2] 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. (Target id: 1988).
• [3] Modulation of Cytotoxicity by Transcription-Coupled Nucleotide Excision Repair Is Independent of the Requirement for Bioactivation of Acylfulvene. Chem Res Toxicol. 2017 Mar 20;30(3):769-776. doi: 10.1021/acs.chemrestox.6b00240. Epub 2017 Feb 16.
• [4] Profiling patterns of glutathione reductase inhibition by the natural product illudin S and its acylfulvene analogues. Mol Biosyst. 2009 Sep;5(9):1013-24.
• [5] Ribosomal S6 kinase (RSK) modulators: a patent review.Expert Opin Ther Pat. 2016 Sep;26(9):1061-78.
• [6] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
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• [10] Cellular inhibition of checkpoint kinase 2 (Chk2) and potentiation of camptothecins and radiation by the novel Chk2 inhibitor PV1019 [7-nitro-1H-indole-2-carboxylic acid {4-[1-(guanidinohydrazone)-ethyl]-phenyl}-amide]. J Pharmacol Exp Ther. 2009 Dec;331(3):816-26.
• [11] CCT241533 Is a Potent and Selective Inhibitor of CHK2 that Potentiates the Cytotoxicity of PARP Inhibitors. Cancer Res. 2011 Jan 15;71(2):463-72.
• [12] A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases. Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20523-8.
• [13] Mechanism of cisplatin proximal tubule toxicity revealed by integrating transcriptomics, proteomics, metabolomics and biokinetics. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):117-27.
• [14] 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.
• [15] Cytotoxic Effects of Cannabinoids on Human HT-29 Colorectal Adenocarcinoma Cells: Different Mechanisms of THC, CBD, and CB83. Int J Mol Sci. 2020 Aug 1;21(15):5533. doi: 10.3390/ijms21155533.
• [16] Comparison of characteristics of peroxide-conditioned immortal human lens-epithelial cell lines with their murine counterparts. Exp Eye Res. 2004 Sep;79(3):411-7.
• [17] Molecular mechanisms of hepatotoxic cholestasis by clavulanic acid: Role of NRF2 and FXR pathways. Food Chem Toxicol. 2021 Dec;158:112664. doi: 10.1016/j.fct.2021.112664. Epub 2021 Nov 9.
• [18] Quercetin modulates Nrf2 and glutathione-related defenses in HepG2 cells: Involvement of p38. Chem Biol Interact. 2012 Jan 25;195(2):154-64.
• [19] Pharmacotoxicology of clinically-relevant concentrations of obeticholic acid in an organotypic human hepatocyte system. Toxicol In Vitro. 2017 Mar;39:93-103.
• [20] Glutathione depletion in antioxidant defense of differentiated NT2-LHON cybrids. Neurobiol Dis. 2007 Mar;25(3):536-44.
• [21] Motexafin gadolinium and zinc induce oxidative stress responses and apoptosis in B-cell lymphoma lines. Cancer Res. 2005 Dec 15;65(24):11676-88.
• [22] An approach to elucidate potential mechanism of renal toxicity of arsenic trioxide. Exp Hematol. 2007 Feb;35(2):252-62.
• [23] Cannabidiol-induced transcriptomic changes and cellular senescence in human Sertoli cells. Toxicol Sci. 2023 Feb 17;191(2):227-238. doi: 10.1093/toxsci/kfac131.
• [24] 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.
• [25] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [26] DNA demethylation by 5-aza-2-deoxycytidine treatment abrogates 17 beta-estradiol-induced cell growth and restores expression of DNA repair genes in human breast cancer cells. Cancer Lett. 2012 Mar;316(1):62-9. doi: 10.1016/j.canlet.2011.10.022. Epub 2011 Oct 23.
• [27] Chronic exposure to arsenic causes increased cell survival, DNA damage, and increased expression of mitochondrial transcription factor A (mtTFA) in human prostate epithelial cells. Chem Res Toxicol. 2011 Mar 21;24(3):340-9. doi: 10.1021/tx1003112. Epub 2011 Jan 14.
• [28] 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.
• [29] Mitochondrial reactive oxygen species are scavenged by Cockayne syndrome B protein in human fibroblasts without nuclear DNA damage. Proc Natl Acad Sci U S A. 2014 Sep 16;111(37):13487-92. doi: 10.1073/pnas.1414135111. Epub 2014 Aug 18.
• [30] The endoperoxide ascaridol shows strong differential cytotoxicity in nucleotide excision repair-deficient cells. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):302-10. doi: 10.1016/j.taap.2012.01.006. Epub 2012 Jan 17.
• [31] Late activation of stress-activated protein kinases/c-Jun N-terminal kinases triggered by cisplatin-induced DNA damage in repair-defective cells. J Biol Chem. 2011 Apr 15;286(15):12991-3001. doi: 10.1074/jbc.M110.190645. Epub 2011 Feb 15.