Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLND7C6)

• DOT Name: Protein FAM43B (FAM43B)
• Gene Name: FAM43B
• Related Disease: Hepatocellular carcinoma
• UniProt ID: FA43B_HUMAN
• Pfam ID: PF14719
• Sequence:
  MLPWRRNKFVLVEDEAKCKAKSLSPGLAYTSLLSSFLRSCPDLLPDWPLERLGRVFRSRR
  QKVELNKEDPTYTVWYLGNAVTLHAKGDGCTDDAVGKIWARCGPGGGTKMKLTLGPHGIR
  MQPCERSAAGGSGGRRPAHAYLLPRITYCTADGRHPRVFAWVYRHQARHKAVVLRCHAVL
  LARAHKARALARLLRQTALAAFSDFKRLQRQSDARHVRQQHLRAGGAAASVPRAPLRRLL
  NAKCAYRPPPSERSRGAPRLSSIQEEDEEEEEDDAEEQEGGVPQRERPEVLSLARELRTC
  SLRGAPAPPPPAQPRRWKAGPRERAGQAR

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Strong	Posttranslational Modification	[1]

13 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 Protein FAM43B (FAM43B).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein FAM43B (FAM43B).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Protein FAM43B (FAM43B).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Protein FAM43B (FAM43B).	[5]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Protein FAM43B (FAM43B).	[6]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Protein FAM43B (FAM43B).	[4]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Protein FAM43B (FAM43B).	[7]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Protein FAM43B (FAM43B).	[8]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Protein FAM43B (FAM43B).	[9]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Protein FAM43B (FAM43B).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Protein FAM43B (FAM43B).	[12]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Protein FAM43B (FAM43B).	[13]
CH-223191	DMMJZYC	Investigative	CH-223191 decreases the expression of Protein FAM43B (FAM43B).	[14]

1 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 increases the methylation of Protein FAM43B (FAM43B).	[10]

References

• [1] Expression of a novel gene FAM43B repressing cell proliferation is regulated by DNA methylation in hepatocellular carcinoma cell lines.Mol Cell Biochem. 2011 Aug;354(1-2):11-20. doi: 10.1007/s11010-011-0800-y. Epub 2011 Apr 2.
• [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] 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] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [5] 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.
• [6] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [7] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [10] 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.
• [11] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [12] 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.
• [13] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
• [14] Adaptive changes in global gene expression profile of lung carcinoma A549 cells acutely exposed to distinct types of AhR ligands. Toxicol Lett. 2018 Aug;292:162-174.