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

General Information of Drug (ID: DMSTJ6Q)

• Drug Name: INX-189 Drug Info
• Synonyms: INX-08032; INX-08189; INX-108; Nucleoside polymerase inhibitors (HCV infection), Cardiff University/Rega Institute; Nucleoside polymerase inhibitors (oral, HCV infection), Inhibitex

Indication

Disease Entry	ICD 11	Status	REF
Hepatitis C virus infection	1E51.1	Phase 2	[1]

• Cross-matching ID:
  PubChem CID: 46700744
  CAS Number: CAS 1234490-83-5
  TTD Drug ID: DMSTJ6Q

Molecule-Related Drug Atlas

Drug(s) Targeting Hepatitis C virus RNA-directed RNA polymerase (HCV NS5B)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PSI-7977	DMLSUWZ	HCV 1-6 infection	1E51	Approved	[4]
Setrobuvir	DMTNDM2	Hepatitis C virus infection	1E51.1	Phase 2	[5]
BI 207127	DMMSGAT	Hepatitis C virus infection	1E51.1	Phase 2	[6]
Valopicitabine dihydrochloride	DMFWZ2U	Virus infection	1A24-1D9Z	Phase 2	[7]
Tegobuvir	DM6YI5T	Hepatitis C virus infection	1E51.1	Phase 2	[8]
VX-759	DMJUSM8	Hepatitis C virus infection	1E51.1	Phase 2	[9]
VX-135	DMZ3FE8	Hepatitis C virus infection	1E51.1	Phase 2	[10]
VX-222	DMO3U4W	Hepatitis C virus infection	1E51.1	Phase 2	[9]
BMS 791325	DMKH4PI	Hepatitis C virus infection	1E51.1	Phase 2	[11]
Filibuvir	DMNSYXB	Hepatitis C virus infection	1E51.1	Phase 2	[12]

Drug(s) Affected By DNA-directed RNA polymerase, mitochondrial (POLRMT)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[13]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[14]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[15]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[16]
Zalcitabine	DMH7MUV	Human immunodeficiency virus infection	1C62	Approved	[16]
Didanosine	DMI2QPE	Human immunodeficiency virus infection	1C62	Approved	[16]
Genistein	DM0JETC	Menopause symptom	GA30.0	Phase 2/3	[15]
Benzo(a)pyrene	DMN7J43	N. A.	N. A.	Phase 1	[17]
QUERCITRIN	DM1DH96	Discovery agent	N.A.	Investigative	[18]

Drug(s) Affected By Cytochrome c oxidase subunit 2 (COX2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[19]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[20]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[21]
Clarithromycin	DM4M1SG	Acute maxillary sinusitis		Approved	[22]
Marinol	DM70IK5	Anorexia nervosa cachexia	6B80	Approved	[23]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[24]
Ivermectin	DMDBX5F	Intestinal strongyloidiasis due to nematode parasite	1F6B	Approved	[25]
Chloramphenicol	DMFXEWT	Bacterial infection	1A00-1C4Z	Approved	[22]
Menthol	DMG2KW7	Back pain	ME84.Z	Approved	[26]
Didanosine	DMI2QPE	Human immunodeficiency virus infection	1C62	Approved	[27]

Drug(s) Affected By NADH-ubiquinone oxidoreductase chain 1 (ND1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[19]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[21]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[28]
Chloramphenicol	DMFXEWT	Bacterial infection	1A00-1C4Z	Approved	[29]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[30]
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[31]
Capsaicin	DMGMF6V	Back pain	ME84.Z	Approved	[32]
Chlorpromazine	DMBGZI3	Acute intermittent hepatic porphyria	5C58.11	Approved	[16]
Haloperidol	DM96SE0	Delirium		Approved	[16]
Thiothixene	DMDINC4	Schizophrenia	6A20	Approved	[16]

Drug(s) Affected By NADH-ubiquinone oxidoreductase chain 5 (ND5)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[21]
Nefazodone	DM4ZS8M	Major depressive disorder	6A70.3	Approved	[33]
Marinol	DM70IK5	Anorexia nervosa cachexia	6B80	Approved	[23]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[28]
Ivermectin	DMDBX5F	Intestinal strongyloidiasis due to nematode parasite	1F6B	Approved	[25]
Cupric Sulfate	DMP0NFQ	Fungal infection	1F29-1F2F	Approved	[34]
Benzo(a)pyrene	DMN7J43	N. A.	N. A.	Phase 1	[35]
THAPSIGARGIN	DMDMQIE	N. A.	N. A.	Preclinical	[36]
3R14S-OCHRATOXIN A	DM2KEW6	Discovery agent	N.A.	Investigative	[37]
bisphenol A	DM2ZLD7	Discovery agent	N.A.	Investigative	[38]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Hepatitis C virus RNA-directed RNA polymerase (HCV NS5B)	TTMVBWH	POLG_HCV1	Inhibitor	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Cytochrome c oxidase subunit 2 (COX2)	OTTMVBJJ	COX2_HUMAN	Gene/Protein Processing	[3]
DNA-directed RNA polymerase, mitochondrial (POLRMT)	OT5Q8ZUJ	RPOM_HUMAN	Gene/Protein Processing	[3]
NADH-ubiquinone oxidoreductase chain 1 (ND1)	OTCLGIXV	NU1M_HUMAN	Gene/Protein Processing	[3]
NADH-ubiquinone oxidoreductase chain 5 (ND5)	OT45LW1K	NU5M_HUMAN	Gene/Protein Processing	[3]

References

• [1] ClinicalTrials.gov (NCT01425970) Chronically-infected HCV Genotype 2 and 3 Treatment-naive Subjects: Part A: Safety and Efficacy of INX-08189 With Peg IFN Alfa-2a and Ribavirin. Part B: INX-08189 in Interferon Free Treatment With Daclatasvir and/or Ribavirin. U.S. National Institutes of Health.
• [2] Clinical pipeline report, company report or official report of Bristol-Myers Squibb.
• [3] Effects of BMS-986094, a Guanosine Nucleotide Analogue, on Mitochondrial DNA Synthesis and Function. Toxicol Sci. 2016 Oct;153(2):396-408. doi: 10.1093/toxsci/kfw135. Epub 2016 Jul 27.
• [4] Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
• [5] Clinical pipeline report, company report or official report of Anadys Pharmaceuticals (2011).
• [6] 2011 Pipeline of Boehringer Ingelheim Pharma.
• [7] Valopicitabine dihydrochloride:a specific polymerase inhibitor of hepatitis C virus. Curr Opin Investig Drugs. 2007 Feb;8(2):150-8.
• [8] Clinical pipeline report, company report or official report of Gilead (2011).
• [9] 2011 Pipeline of Vertex.
• [10] All-oral HCV therapies near approval. Nat Rev Drug Discov. 2013 Jun;12(6):409-11.
• [11] 2011 Pipeline of Bristol-Myers Squibb.
• [12] Clinical pipeline report, company report or official report of Pfizer (2011).
• [13] 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.
• [14] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [15] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [16] 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.
• [17] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [18] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.
• [19] Tea polyphenols ameliorates neural redox imbalance and mitochondrial dysfunction via mechanisms linking the key circadian regular Bmal1. Food Chem Toxicol. 2017 Dec;110:189-199. doi: 10.1016/j.fct.2017.10.031. Epub 2017 Oct 20.
• [20] Quantitative proteomic analysis of HepG2 cells treated with quercetin suggests IQGAP1 involved in quercetin-induced regulation of cell proliferation and migration. OMICS. 2009 Apr;13(2):93-103. doi: 10.1089/omi.2008.0075.
• [21] Morphological and molecular course of mitochondrial pathology in cultured human cells exposed long-term to Zidovudine. Environ Mol Mutagen. 2007 Apr-May;48(3-4):179-89. doi: 10.1002/em.20245.
• [22] A genome-wide analysis of targets of macrolide antibiotics in mammalian cells. J Biol Chem. 2020 Feb 14;295(7):2057-2067. doi: 10.1074/jbc.RA119.010770. Epub 2020 Jan 8.
• [23] Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans. Sci Rep. 2020 Feb 26;10(1):3450. doi: 10.1038/s41598-020-59827-1.
• [24] Nuclear and Mitochondrial DNA Methylation Patterns Induced by Valproic Acid in Human Hepatocytes. Chem Res Toxicol. 2017 Oct 16;30(10):1847-1854. doi: 10.1021/acs.chemrestox.7b00171. Epub 2017 Sep 13.
• [25] 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.
• [26] Pod-based menthol and tobacco flavored e-cigarettes cause mitochondrial dysfunction in lung epithelial cells. Toxicol Lett. 2020 Oct 15;333:303-311. doi: 10.1016/j.toxlet.2020.08.003. Epub 2020 Aug 9.
• [27] In vitro cytotoxicity and mitochondrial toxicity of tenofovir alone and in combination with other antiretrovirals in human renal proximal tubule cells. Antimicrob Agents Chemother. 2006 Nov;50(11):3824-32. doi: 10.1128/AAC.00437-06. Epub 2006 Aug 28.
• [28] Integrated 'omics analysis reveals new drug-induced mitochondrial perturbations in human hepatocytes. Toxicol Lett. 2018 Jun 1;289:1-13.
• [29] The effect of ethidium bromide and chloramphenicol on mitochondrial biogenesis in primary human fibroblasts. Toxicol Appl Pharmacol. 2012 May 15;261(1):42-9. doi: 10.1016/j.taap.2012.03.009.
• [30] Human 3D multicellular microtissues: an upgraded model for the in vitro mechanistic investigation of inflammation-associated drug toxicity. Toxicol Lett. 2019 Sep 15;312:34-44.
• [31] 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.
• [32] Food derived respiratory complex I inhibitors modify the effect of Leber hereditary optic neuropathy mutations. Food Chem Toxicol. 2018 Oct;120:89-97. doi: 10.1016/j.fct.2018.07.014. Epub 2018 Jul 6.
• [33] Involvement of mitochondrial dysfunction in nefazodone-induced hepatotoxicity. Food Chem Toxicol. 2016 Aug;94:148-58. doi: 10.1016/j.fct.2016.06.001. Epub 2016 Jun 8.
• [34] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [35] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [36] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [37] In vitro blood brain barrier exposure to mycotoxins and carotenoids pumpkin extract alters mitochondrial gene expression and oxidative stress. Food Chem Toxicol. 2021 Jul;153:112261. doi: 10.1016/j.fct.2021.112261. Epub 2021 May 17.
• [38] Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.