Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPMOJ7W)

• DOT Name: Chromosome transmission fidelity protein 8 homolog (CHTF8)
• Synonyms: hCTF8
• Gene Name: CHTF8
• UniProt ID: CTF8_HUMAN
• Pfam ID: PF09696
• Sequence:
  MVQIVISSARAGGLAEWVLMELQGEIEARYSTGLAGNLLGDLHYTTEGIPVLIVGHHILY
  GKIIHLEKPFAVLVKHTPGDQDCDELGRETGTRYLVTALIKDKILFKTRPKPIITSVPKK
  V
• Function: Chromosome cohesion factor involved in sister chromatid cohesion and fidelity of chromosome transmission. Component of one of the cell nuclear antigen loader complexes, CTF18-replication factor C (CTF18-RFC), which consists of CTF18, CTF8, DSCC1, RFC2, RFC3, RFC4 and RFC5. The CTF18-RFC complex binds to single-stranded and primed DNAs and has weak ATPase activity that is stimulated the presence of primed DNA, replication protein A (RPA) and proliferating cell nuclear antigen (PCNA). The CTF18-RFC complex catalyzes the ATP-dependent loading of PCNA onto primed and gapped DNA. It also interacts with and stimulates POLH, which is suggestive of a protein network that coordinates DNA repair, recombination and chromosome cohesion reactions with replication fork progression.
• Reactome Pathway: Polymerase switching on the C-strand of the telomere (R-HSA-174411)

Molecular Interaction Atlas (MIA) of This DOT

8 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Chromosome transmission fidelity protein 8 homolog (CHTF8).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Chromosome transmission fidelity protein 8 homolog (CHTF8).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Chromosome transmission fidelity protein 8 homolog (CHTF8).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Chromosome transmission fidelity protein 8 homolog (CHTF8).	[4]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Chromosome transmission fidelity protein 8 homolog (CHTF8).	[5]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Chromosome transmission fidelity protein 8 homolog (CHTF8).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Chromosome transmission fidelity protein 8 homolog (CHTF8).	[7]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Chromosome transmission fidelity protein 8 homolog (CHTF8).	[8]

References

• [1] 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.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] 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.
• [4] 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.
• [5] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [6] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [7] Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.
• [8] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.