Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSVT07B)

• DOT Name: Fibrinogen C domain-containing protein 1 (FIBCD1)
• Gene Name: FIBCD1
• Related Disease:
  Gastric cancer
  Stomach cancer
• UniProt ID: FBCD1_HUMAN
• PDB ID: 4M7F; 4M7H; 6ZQR; 6ZQX; 6ZQY; 6ZR0; 6ZR3; 6ZR4
• Pfam ID: PF00147
• Sequence:
  MVNDRWKTMGGAAQLEDRPRDKPQRPSCGYVLCTVLLALAVLLAVAVTGAVLFLNHAHAP
  GTAPPPVVSTGAASANSALVTVERADSSHLSILIDPRCPDLTDSFARLESAQASVLQALT
  EHQAQPRLVGDQEQELLDTLADQLPRLLARASELQTECMGLRKGHGTLGQGLSALQSEQG
  RLIQLLSESQGHMAHLVNSVSDILDALQRDRGLGRPRNKADLQRAPARGTRPRGCATGSR
  PRDCLDVLLSGQQDDGVYSVFPTHYPAGFQVYCDMRTDGGGWTVFQRREDGSVNFFRGWD
  AYRDGFGRLTGEHWLGLKRIHALTTQAAYELHVDLEDFENGTAYARYGSFGVGLFSVDPE
  EDGYPLTVADYSGTAGDSLLKHSGMRFTTKDRDSDHSENNCAAFYRGAWWYRNCHTSNLN
  GQYLRGAHASYADGVEWSSWTGWQYSLKFSEMKIRPVREDR
• Function: Acetyl group-binding receptor which shows a high-affinity and calcium-dependent binding to acetylated structures such as chitin, some N-acetylated carbohydrates, and amino acids, but not to their non-acetylated counterparts. Can facilitate the endocytosis of acetylated components.
• Tissue Specificity: Expressed in the small and large intestinal epithelial cells with a highly polarized localization to the apical surface corresponding to the brush border and in the ducts of the salivary gland.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Gastric cancer	DISXGOUK	Limited	Altered Expression	[1]
Stomach cancer	DISKIJSX	Limited	Altered Expression	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Fibrinogen C domain-containing protein 1 (FIBCD1).	[2]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Fibrinogen C domain-containing protein 1 (FIBCD1).	[3]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Fibrinogen C domain-containing protein 1 (FIBCD1).	[4]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Fibrinogen C domain-containing protein 1 (FIBCD1).	[5]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Fibrinogen C domain-containing protein 1 (FIBCD1).	[6]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Fibrinogen C domain-containing protein 1 (FIBCD1).	[7]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of Fibrinogen C domain-containing protein 1 (FIBCD1).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Fibrinogen C domain-containing protein 1 (FIBCD1).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Fibrinogen C domain-containing protein 1 (FIBCD1).	[9]

References

• [1] Overexpression of FIBCD1 Is Predictive of Poor Prognosis in Gastric Cancer.Am J Clin Pathol. 2018 Apr 25;149(6):474-483. doi: 10.1093/ajcp/aqy013.
• [2] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [3] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [4] New insights into the mechanisms underlying 5-fluorouracil-induced intestinal toxicity based on transcriptomic and metabolomic responses in human intestinal organoids. Arch Toxicol. 2021 Aug;95(8):2691-2718. doi: 10.1007/s00204-021-03092-2. Epub 2021 Jun 20.
• [5] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [6] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [7] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [8] 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.
• [9] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [10] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.