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

General Information of Drug (ID: DMCDTIG)

• Drug Name: 680C91 Drug Info
• Synonyms: 163239-22-3; CHEMBL355606; 6-Fluoro-3-((E)-2-pyridin-3-yl-vinyl)-1H-indole; 6-fluoro-3-[(E)-2-pyridin-3-ylethenyl]-1H-indole; SCHEMBL3262721; SCHEMBL3262726; ZINC19965; CHEBI:131851; EX-A4573; BDBM50289137; s8997; AKOS024458137; 680C91, >=98% (HPLC); 680C-91; (e)-6-fluoro-3-[2-(3-pyridyl)vinyl]-1h-indole; (E)-6-Fluoro-3-(2-(pyridin-3-yl)vinyl)-1H-indole; 6-fluoro-3-[(E)-2-(pyridin-3-yl)vinyl]-1H-indole; Q27225279; 6-Fluoro-3-[(1E)-2-(3-pyridinyl)ethenyl]-1H-indole; 1H-Indole, 6-fluoro-3-[(1E)-2-(3-pyridinyl)ethenyl]-

Indication

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

• Cross-matching ID:
  PubChem CID: 10014426
  ChEBI ID: CHEBI:131851
  CAS Number: CAS 163239-22-3
  TTD Drug ID: DMCDTIG

Molecule-Related Drug Atlas

Drug(s) Targeting Tryptophan 2,3-dioxygenase (TDO)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
DN1406131	DMQFX8R	Solid tumour/cancer	2A00-2F9Z	Phase 1	[4]
HTI-1090	DMI4TEC	Solid tumour/cancer	2A00-2F9Z	Phase 1	[5]
2,3-diamino-benzo[b]thiophene derivative 4	DMEDFNC	N. A.	N. A.	Patented	[6]
PMID27172114-Compound-30	DMBWLSA	N. A.	N. A.	Patented	[6]
2,3-diamino-benzo[b]thiophene derivative 2	DMDYXKT	N. A.	N. A.	Patented	[6]
2,3-diamino-benzo[b]thiophene derivative 8	DM5O8K0	N. A.	N. A.	Patented	[6]
2,3-diamino-benzo[b]thiophene derivative 7	DMQVMNJ	N. A.	N. A.	Patented	[6]
2,3-diamino-benzo[b]thiophene derivative 6	DMINE6V	N. A.	N. A.	Patented	[6]
2,3-diamino-benzo[b]thiophene derivative 5	DM05WXD	N. A.	N. A.	Patented	[6]
2,3-diamino-benzo[b]thiophene derivative 1	DMD2KRW	N. A.	N. A.	Patented	[6]

Drug(s) Affected By Histone H2AX (H2AX)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[7]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[8]
Selenium	DM25CGV	N. A.	N. A.	Approved	[9]
Ribavirin	DMEYLH9	Hepatitis C virus infection	1E51.1	Approved	[10]
Etretinate	DM2CZFA	Keratosis	ED56	Approved	[11]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[12]
Dactinomycin	DM2YGNW	Adult kidney Wilms tumor		Approved	[13]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[14]
Lapatinib	DM3BH1Y	Breast cancer	2C60-2C65	Approved	[15]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[16]

Drug(s) Affected By DNA polymerase kappa (POLK)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[17]
Clorgyline	DMCEUJD	Parkinson disease	8A00.0	Approved	[18]
Paclitaxel	DMLB81S	Breast carcinoma		Approved	[19]
Cupric Sulfate	DMP0NFQ	Fungal infection	1F29-1F2F	Approved	[20]
Irinotecan	DMP6SC2	Adenocarcinoma	2D40	Approved	[21]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[22]
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[23]
Guanine	DMIWLJE	N. A.	N. A.	Phase 3	[24]
TAK-243	DM4GKV2	Solid tumour/cancer	2A00-2F9Z	Phase 1	[25]
MK-886	DMT0O7H	Asthma	CA23	Discontinued in Phase 2	[26]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Tryptophan 2,3-dioxygenase (TDO)	TTXNCBV	T23O_HUMAN	Inhibitor	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
DNA polymerase kappa (POLK)	OTKZ38JH	POLK_HUMAN	Gene/Protein Processing	[3]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Gene/Protein Processing	[3]

References

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• [2] Effects of IDO1 and TDO2 inhibition on cognitive deficits and anxiety following LPS-induced neuroinflammation. Acta Neuropsychiatr. 2020 Feb;32(1):43-53.
• [3] Kynurenine Signaling Increases DNA Polymerase Kappa Expression and Promotes Genomic Instability in Glioblastoma Cells. Chem Res Toxicol. 2016 Jan 19;29(1):101-8. doi: 10.1021/acs.chemrestox.5b00452. Epub 2015 Dec 30.
• [4] ClinicalTrials.gov (NCT03641794) Indoleamine 2,3-Dioxygenase (IDO) Inhibitor in Healthy Volunteers. U.S. National Institutes of Health.
• [5] Discovery of cyanopyridine scaffold as novel indoleamine-2,3-dioxygenase 1 (IDO1) inhibitors through virtual screening and preliminary hit optimisation. J Enzyme Inhib Med Chem. 2019 Dec;34(1):250-263.
• [6] Inhibitors of the kynurenine pathway as neurotherapeutics: a patent review (2012-2015).Expert Opin Ther Pat. 2016 Jul;26(7):815-32.
• [7] Cannabinoids synergize with carfilzomib, reducing multiple myeloma cells viability and migration. Oncotarget. 2016 Nov 22;7(47):77543-77557. doi: 10.18632/oncotarget.12721.
• [8] Hsa-let-7g miRNA regulates the anti-tumor effects of gastric cancer cells under oxidative stress through the expression of DDR genes. J Toxicol Sci. 2015 Jun;40(3):329-38. doi: 10.2131/jts.40.329.
• [9] 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.
• [10] Inhibition of cardiomyocyte differentiation of human induced pluripotent stem cells by Ribavirin: Implication for its cardiac developmental toxicity. Toxicology. 2020 Apr 15;435:152422. doi: 10.1016/j.tox.2020.152422. Epub 2020 Feb 26.
• [11] Synthesis and structure-activity relationships of new antiproliferative and proapoptotic retinoid-related biphenyl-4-yl-acrylic acids. Bioorg Med Chem. 2007 Jul 15;15(14):4863-75. doi: 10.1016/j.bmc.2007.04.057. Epub 2007 May 3.
• [12] Methotrexate induces apoptosis through p53/p21-dependent pathway and increases E-cadherin expression through downregulation of HDAC/EZH2. Biochem Pharmacol. 2011 Feb 15;81(4):510-7. doi: 10.1016/j.bcp.2010.11.014. Epub 2010 Nov 27.
• [13] Actinomycin D inhibits the expression of the cystine/glutamate transporter xCT via attenuation of CD133 synthesis in CD133(+) HCC. Chem Biol Interact. 2019 Aug 25;309:108713. doi: 10.1016/j.cbi.2019.06.026. Epub 2019 Jun 19.
• [14] Simvastatin and purine analogs have a synergic effect on apoptosis of chronic lymphocytic leukemia cells. Ann Hematol. 2010 Nov;89(11):1115-24. doi: 10.1007/s00277-010-0988-z. Epub 2010 May 25.
• [15] The involvement of hepatic cytochrome P450s in the cytotoxicity of lapatinib. Toxicol Sci. 2023 Dec 21;197(1):69-78. doi: 10.1093/toxsci/kfad099.
• [16] The isoflavonoids genistein and quercetin activate different stress signaling pathways as shown by analysis of site-specific phosphorylation of ATM, p53 and histone H2AX. DNA Repair (Amst). 2004 Mar 4;3(3):235-44. doi: 10.1016/j.dnarep.2003.10.014.
• [17] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [18] Anti-oncogenic and pro-differentiation effects of clorgyline, a monoamine oxidase A inhibitor, on high grade prostate cancer cells. BMC Med Genomics. 2009 Aug 20;2:55. doi: 10.1186/1755-8794-2-55.
• [19] Effects of paclitaxel on proliferation and apoptosis in human acute myeloid leukemia HL-60 cells. Acta Pharmacol Sin. 2004 Mar;25(3):378-84.
• [20] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [21] Clinical determinants of response to irinotecan-based therapy derived from cell line models. Clin Cancer Res. 2008 Oct 15;14(20):6647-55.
• [22] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [23] 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.
• [24] Analysis of nucleotide insertion opposite 2,2,4-triamino-5(2H)-oxazolone by eukaryotic B- and Y-family DNA polymerases. Chem Res Toxicol. 2015 Jun 15;28(6):1307-16. doi: 10.1021/acs.chemrestox.5b00114. Epub 2015 Jun 3.
• [25] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [26] Leukotriene biosynthesis inhibitor MK886 impedes DNA polymerase activity. Chem Res Toxicol. 2013 Feb 18;26(2):221-32. doi: 10.1021/tx300392m. Epub 2013 Jan 31.