Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9MG9IS)

• DOT Name: Uncharacterized protein C9orf40 (C9ORF40)
• Gene Name: C9ORF40
• UniProt ID: CI040_HUMAN
• Pfam ID: PF15017
• Sequence:
  MAKRRAAEPVTFHVPWKRLLLCDFAEQPPPPPLWIRPPGVAHAGQLLGVPEQHRKRKIDA
  GTMAEPSASPSKRRDSGDNSAPSGQEREDHGLETGDPPLPPPPVLPGPGEELPGARLPGG
  GGDDGAGRAGPPRGDWGVASRQHNEEFWQYNTFQYWRNPLPPIDLADIEDLSEDTLTEAT
  LQGRNEGAEVDMES

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Uncharacterized protein C9orf40 (C9ORF40).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Uncharacterized protein C9orf40 (C9ORF40).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Uncharacterized protein C9orf40 (C9ORF40).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Uncharacterized protein C9orf40 (C9ORF40).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Uncharacterized protein C9orf40 (C9ORF40).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Uncharacterized protein C9orf40 (C9ORF40).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Uncharacterized protein C9orf40 (C9ORF40).	[7]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Uncharacterized protein C9orf40 (C9ORF40).	[7]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Uncharacterized protein C9orf40 (C9ORF40).	[8]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Uncharacterized protein C9orf40 (C9ORF40).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Uncharacterized protein C9orf40 (C9ORF40).	[10]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Uncharacterized protein C9orf40 (C9ORF40).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Uncharacterized protein C9orf40 (C9ORF40).	[11]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [7] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [8] Gene expression profiling in Ishikawa cells: a fingerprint for estrogen active compounds. Toxicol Appl Pharmacol. 2009 Apr 1;236(1):85-96.
• [9] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [10] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [11] 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.
• [12] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.