Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT87I374)

• DOT Name: Tubulin epsilon and delta complex protein 2 (TEDC2)
• Gene Name: TEDC2
• Related Disease: Hepatocellular carcinoma
• UniProt ID: TEDC2_HUMAN
• Pfam ID: PF15764
• Sequence:
  MLPAGCSRRLVAELQGALDACAQRQLQLEQSLRVCRRLLHAWEPTGTRALKPPPGPETNG
  EDPLPACTPSPQDLKELEFLTQALEKAVRVRRGITKAGERDKAPSLKSRSIVTSSGTTAS
  APPHSPGQAGGHASDTRPTKGLRQTTVPAKGHPERRLLSVGDGTRVGMGARTPRPGAGLR
  DQQMAPSAAPQAPEAFTLKEKGHLLRLPAAFRKAASQNSSLWAQLSSTQTSDSTDAAAAK
  TQFLQNMQTASGGPQPRLSAVEVEAEAGRLRKACSLLRLRMREELSAAPMDWMQEYRCLL
  TLEGLQAMVGQCLHRLQELRAAVAEQPPRPCPVGRPPGASPSCGGRAEPAWSPQLLVYSS
  TQELQTLAALKLRVAVLDQQIHLEKVLMAELLPLVSAAQPQGPPWLALCRAVHSLLCEGG
  ARVLTILRDEPAV
• Function: Acts as a positive regulator of ciliary hedgehog signaling. Required for centriole stability.

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	Definitive	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Tubulin epsilon and delta complex protein 2 (TEDC2).	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Tubulin epsilon and delta complex protein 2 (TEDC2).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Tubulin epsilon and delta complex protein 2 (TEDC2).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Tubulin epsilon and delta complex protein 2 (TEDC2).	[5]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Tubulin epsilon and delta complex protein 2 (TEDC2).	[6]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Tubulin epsilon and delta complex protein 2 (TEDC2).	[6]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Tubulin epsilon and delta complex protein 2 (TEDC2).	[7]
GSK2110183	DMZHB37	Phase 2	GSK2110183 decreases the expression of Tubulin epsilon and delta complex protein 2 (TEDC2).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Tubulin epsilon and delta complex protein 2 (TEDC2).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Tubulin epsilon and delta complex protein 2 (TEDC2).	[10]

References

• [1] Computational discovery of niclosamide ethanolamine, a repurposed drug candidate that reduces growth of hepatocellular carcinoma cells initro and in mice by inhibiting cell division cycle 37 signaling. Gastroenterology. 2017 Jun;152(8):2022-2036.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [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] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [9] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [10] 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.