Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYSXAX6)

• DOT Name: Cleavage stimulation factor subunit 1 (CSTF1)
• Synonyms: CF-1 50 kDa subunit; Cleavage stimulation factor 50 kDa subunit; CSTF 50 kDa subunit; CstF-50
• Gene Name: CSTF1
• Related Disease:
  Breast cancer
  Breast carcinoma
• UniProt ID: CSTF1_HUMAN
• PDB ID: 6B3X
• Pfam ID: PF16699 ; PF00400
• Sequence:
  MYRTKVGLKDRQQLYKLIISQLLYDGYISIANGLINEIKPQSVCAPSEQLLHLIKLGMEN
  DDTAVQYAIGRSDTVAPGTGIDLEFDADVQTMSPEASEYETCYVTSHKGPCRVATYSRDG
  QLIATGSADASIKILDTERMLAKSAMPIEVMMNETAQQNMENHPVIRTLYDHVDEVTCLA
  FHPTEQILASGSRDYTLKLFDYSKPSAKRAFKYIQEAEMLRSISFHPSGDFILVGTQHPT
  LRLYDINTFQCFVSCNPQDQHTDAICSVNYNSSANMYVTGSKDGCIKLWDGVSNRCITTF
  EKAHDGAEVCSAIFSKNSKYILSSGKDSVAKLWEISTGRTLVRYTGAGLSGRQVHRTQAV
  FNHTEDYVLLPDERTISLCCWDSRTAERRNLLSLGHNNIVRCIVHSPTNPGFMTCSDDFR
  ARFWYRRSTTD
• Function: One of the multiple factors required for polyadenylation and 3'-end cleavage of mammalian pre-mRNAs. May be responsible for the interaction of CSTF with other factors to form a stable complex on the pre-mRNA.
• KEGG Pathway: mR. surveillance pathway (hsa03015)
• Reactome Pathway:
  Processing of Capped Intron-Containing Pre-mRNA (R-HSA-72203)
  RNA Polymerase II Transcription Termination (R-HSA-73856)
  Processing of Intronless Pre-mRNAs (R-HSA-77595)
  mRNA 3'-end processing (R-HSA-72187)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[1]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[1]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Cleavage stimulation factor subunit 1 (CSTF1).	[2]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Cleavage stimulation factor subunit 1 (CSTF1).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Cleavage stimulation factor subunit 1 (CSTF1).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Cleavage stimulation factor subunit 1 (CSTF1).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Cleavage stimulation factor subunit 1 (CSTF1).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Cleavage stimulation factor subunit 1 (CSTF1).	[6]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Cleavage stimulation factor subunit 1 (CSTF1).	[7]
Clozapine	DMFC71L	Approved	Clozapine decreases the expression of Cleavage stimulation factor subunit 1 (CSTF1).	[8]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Cleavage stimulation factor subunit 1 (CSTF1).	[10]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Cleavage stimulation factor subunit 1 (CSTF1).	[11]

References

• [1] Assessing associations between the AURKA-HMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers.PLoS One. 2015 Apr 1;10(4):e0120020. doi: 10.1371/journal.pone.0120020. eCollection 2015.
• [2] 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.
• [3] 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.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] 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.
• [7] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [8] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [9] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [10] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [11] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.