Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDXQCS5)

• DOT Name: Protein FAM168A (FAM168A)
• Synonyms: Tongue cancer chemotherapy resistance-associated protein 1
• Gene Name: FAM168A
• Related Disease:
  Advanced cancer
  Epithelial ovarian cancer
  Gastric cancer
  Gastric neoplasm
  Hereditary diffuse gastric adenocarcinoma
  Ovarian cancer
  Ovarian neoplasm
  Squamous cell carcinoma
  Hepatocellular carcinoma
  Lung cancer
  Lung carcinoma
  leukaemia
  Leukemia
  Neoplasm
• UniProt ID: F168A_HUMAN
• Pfam ID: PF14944
• Sequence:
  MNPVYSPVQPGAPYGNPKNMAYTGYPTAYPAAAPAYNPSLYPTNSPSYAPEFQFLHSAYA
  TLLMKQAWPQNSSSCGTEGTFHLPVDTGTENRTYQASSAAFRYTAGTPYKVPPTQSNTAP
  PPYSPSPNPYQTAMYPIRSAYPQQNLYAQGAYYTQPVYAAQPHVIHHTTVVQPNSIPSAI
  YPAPVAAPRTNGVAMGMVAGTTMAMSAGTLLTTPQHTAIGAHPVSMPTYRAQGTPAYSYV
  PPHW
• Function: In cancer context, protects cells from induced-DNA damage and apoptosis. Acts, at least in part, through PI3K/AKT/NFKB signaling pathway and by preventing POLB degradation. Decreases POLB ubiquitation and stabilizes its protein levels.

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[2]
Gastric cancer	DISXGOUK	Strong	Biomarker	[3]
Gastric neoplasm	DISOKN4Y	Strong	Biomarker	[3]
Hereditary diffuse gastric adenocarcinoma	DISUIBYS	Strong	Biomarker	[3]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[2]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[2]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[4]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[5]
Lung cancer	DISCM4YA	moderate	Altered Expression	[1]
Lung carcinoma	DISTR26C	moderate	Altered Expression	[1]
leukaemia	DISS7D1V	Limited	Biomarker	[6]
Leukemia	DISNAKFL	Limited	Biomarker	[6]
Neoplasm	DISZKGEW	Limited	Biomarker	[6]

9 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 Protein FAM168A (FAM168A).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Protein FAM168A (FAM168A).	[8]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Protein FAM168A (FAM168A).	[9]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Protein FAM168A (FAM168A).	[10]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Protein FAM168A (FAM168A).	[11]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Protein FAM168A (FAM168A).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Protein FAM168A (FAM168A).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Protein FAM168A (FAM168A).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Protein FAM168A (FAM168A).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Protein FAM168A (FAM168A).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Protein FAM168A (FAM168A).	[15]

References

• [1] TCRP1 promotes NIH/3T3 cell transformation by over-activating PDK1 and AKT1.Oncogenesis. 2017 Apr 24;6(4):e323. doi: 10.1038/oncsis.2017.18.
• [2] TCRP1 expression is associated with platinum sensitivity in human lung and ovarian cancer cells.Oncol Lett. 2017 Mar;13(3):1398-1405. doi: 10.3892/ol.2016.5534. Epub 2016 Dec 27.
• [3] A gene expression signature of acquired chemoresistance to cisplatin and fluorouracil combination chemotherapy in gastric cancer patients.PLoS One. 2011 Feb 18;6(2):e16694. doi: 10.1371/journal.pone.0016694.
• [4] Microarray-assisted pathway analysis identifies MT1X & NFB as mediators of TCRP1-associated resistance to cisplatin in oral squamous cell carcinoma.PLoS One. 2012;7(12):e51413. doi: 10.1371/journal.pone.0051413. Epub 2012 Dec 10.
• [5] Lycorine Promotes Autophagy and Apoptosis via TCRP1/Akt/mTOR Axis Inactivation in Human Hepatocellular Carcinoma.Mol Cancer Ther. 2017 Dec;16(12):2711-2723. doi: 10.1158/1535-7163.MCT-17-0498. Epub 2017 Sep 28.
• [6] FAM168A participates in the development of chronic myeloid leukemia via BCR-ABL1/AKT1/NFB pathway.BMC Cancer. 2019 Jul 10;19(1):679. doi: 10.1186/s12885-019-5898-4.
• [7] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [8] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [9] Changes in gene expressions elicited by physiological concentrations of genistein on human endometrial cancer cells. Mol Carcinog. 2006 Oct;45(10):752-63.
• [10] 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.
• [11] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [12] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [13] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [14] 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.
• [15] 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.
• [16] 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.