Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAK119S)

• DOT Name: LIX1-like protein (LIX1L)
• Gene Name: LIX1L
• Related Disease: Hepatocellular carcinoma
• UniProt ID: LIX1L_HUMAN
• Pfam ID: PF14954
• Sequence:
  METMRAQRLQPGVGTSGRGTLRALRPGVTGAAAATATPPAGPPPAPPPPAPPPPPLLLSG
  APGLPLPPGAAGSPAVLREAVEAVVRSFAKHTQGYGRVNVVEALQEFWQMKQSRGADLKN
  GALVVYEMVPSNSPPYVCYVTLPGGSCFGSFQFCPTKAEARRSAAKIALMNSVFNEHPSR
  RITDEFIEKSVSEALASFNGNREEADNPNTGIGAFRFMLESNKGKSMLEFQELMTVFQLL
  HWNGSLKAMRERQCSRQEVLAHYSHRALDDDIRHQMALDWVSREQSVPGALSRELASTER
  ELDEARLAGKELRFHKEKKDILVLAAGQLGNMHSSNC

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]

9 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 LIX1-like protein (LIX1L).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of LIX1-like protein (LIX1L).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of LIX1-like protein (LIX1L).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of LIX1-like protein (LIX1L).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of LIX1-like protein (LIX1L).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of LIX1-like protein (LIX1L).	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of LIX1-like protein (LIX1L).	[8]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of LIX1-like protein (LIX1L).	[6]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of LIX1-like protein (LIX1L).	[10]

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 affects the methylation of LIX1-like protein (LIX1L).	[9]

References

• [1] LncRNA TATDN1 induces the progression of hepatocellular carcinoma via targeting miRNA-6089.Eur Rev Med Pharmacol Sci. 2019 Aug;23(15):6459-6466. doi: 10.26355/eurrev_201908_18529.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [4] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] 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.
• [7] 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.
• [8] Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells. Toxicol Appl Pharmacol. 2012 Jun 1;261(2):204-16.
• [9] 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.
• [10] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.