Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZ8A9L3)

• DOT Name: Myc target protein 1 (MYCT1)
• Synonyms: Myc target in myeloid cells protein 1
• Gene Name: MYCT1
• Related Disease:
  Gastric neoplasm
  Hepatocellular carcinoma
  IgA nephropathy
  Laryngeal squamous cell carcinoma
  Neoplasm
  Stomach cancer
  Acute myelogenous leukaemia
  B-cell neoplasm
• UniProt ID: MYCT1_HUMAN
• Pfam ID: PF15179
• Sequence:
  MRTQVYEGLCKNYFSLAVLQRDRIKLLFFDILVFLSVFLLFLLFLVDIMANNTTSLGSPW
  PENFWEDLIMSFTVSMAIGLVLGGFIWAVFICLSRRRRASAPISQWSSSRRSRSSYTHGL
  NRTGFYRHSGCERRSNLSLASLTFQRQASLEQANSFPRKSSFRASTFHPFLQCPPLPVET
  ESQLVTLPSSNISPTISTSHSLSRPDYWSSNSLRVGLSTPPPPAYESIIKAFPDS
• Function: May regulate certain MYC target genes, MYC seems to be a direct upstream transcriptional activator. Does not seem to significantly affect growth cell capacity. Overexpression seems to mediate many of the known phenotypic features associated with MYC, including promotion of apoptosis, alteration of morphology, enhancement of anchorage-independent growth, tumorigenic conversion, promotion of genomic instability, and inhibition of hematopoietic differentiation.
• Tissue Specificity: Down-regulated in gastric cancer tissues.

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Gastric neoplasm	DISOKN4Y	Strong	Altered Expression	[1]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[2]
IgA nephropathy	DISZ8MTK	Strong	Genetic Variation	[3]
Laryngeal squamous cell carcinoma	DIS9UUVF	Strong	Biomarker	[4]
Neoplasm	DISZKGEW	Strong	Biomarker	[4]
Stomach cancer	DISKIJSX	Strong	Posttranslational Modification	[1]
Acute myelogenous leukaemia	DISCSPTN	moderate	Altered Expression	[4]
B-cell neoplasm	DISVY326	moderate	Altered Expression	[4]

2 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 Myc target protein 1 (MYCT1).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Myc target protein 1 (MYCT1).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Myc target protein 1 (MYCT1).	[6]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Myc target protein 1 (MYCT1).	[7]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of Myc target protein 1 (MYCT1).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Myc target protein 1 (MYCT1).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Myc target protein 1 (MYCT1).	[11]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride increases the expression of Myc target protein 1 (MYCT1).	[12]

References

• [1] Expression of MTLC gene in gastric carcinoma.World J Gastroenterol. 2003 Oct;9(10):2160-3. doi: 10.3748/wjg.v9.i10.2160.
• [2] miR-632 Functions as Oncogene in Hepatocellular Carcinoma via Targeting MYCT1.Hum Gene Ther Clin Dev. 2019 Jun;30(2):67-73. doi: 10.1089/humc.2019.040. Epub 2019 May 8.
• [3] Novel genes and variants associated with IgA nephropathy by co-segregating with the disease phenotypes in 10 IgAN families.Gene. 2015 Oct 15;571(1):43-51. doi: 10.1016/j.gene.2015.06.041. Epub 2015 Jun 18.
• [4] Overexpression of MYCT1 Inhibits Proliferation and Induces Apoptosis in Human Acute Myeloid Leukemia HL-60 and KG-1a Cells in vitro and in vivo.Front Pharmacol. 2018 Sep 18;9:1045. doi: 10.3389/fphar.2018.01045. eCollection 2018.
• [5] 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.
• [6] 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.
• [7] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [8] Gene expression signatures after ethanol exposure in differentiating embryoid bodies. Toxicol In Vitro. 2018 Feb;46:66-76.
• [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] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [11] 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.
• [12] Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development. PLoS One. 2013;8(3):e58822.