Details of Drug Off-Target (DOT)

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

• DOT Name: COMM domain-containing protein 6 (COMMD6)
• Gene Name: COMMD6
• Related Disease:
  Cholangiocarcinoma
  Head-neck squamous cell carcinoma
  Neoplasm
  Non-small-cell lung cancer
• UniProt ID: COMD6_HUMAN
• PDB ID: 8F2R; 8F2U
• Pfam ID: PF07258
• Sequence:
  MEASSEPPLDAKSDVTNQLVDFQWKLGMAVSSDTCRSLKYPYVAVMLKVADHSGQVKTKC
  FEMTIPQFQNFYRQFKEIAAVIETV
• Function: May modulate activity of cullin-RING E3 ubiquitin ligase (CRL) complexes. Down-regulates activation of NF-kappa-B. Inhibits TNF-induced NFKB1 activation.
• Tissue Specificity: Ubiquitous. Expressed in brain, heart, skeletal muscle, lung, pancreas, liver, kidney, small intestine and placenta.
• Reactome Pathway: Neddylation (R-HSA-8951664)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cholangiocarcinoma	DIS71F6X	Strong	Altered Expression	[1]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of COMM domain-containing protein 6 (COMMD6).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of COMM domain-containing protein 6 (COMMD6).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of COMM domain-containing protein 6 (COMMD6).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of COMM domain-containing protein 6 (COMMD6).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of COMM domain-containing protein 6 (COMMD6).	[7]
Irinotecan	DMP6SC2	Approved	Irinotecan increases the expression of COMM domain-containing protein 6 (COMMD6).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of COMM domain-containing protein 6 (COMMD6).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of COMM domain-containing protein 6 (COMMD6).	[10]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of COMM domain-containing protein 6 (COMMD6).	[11]
chloropicrin	DMSGBQA	Investigative	chloropicrin affects the expression of COMM domain-containing protein 6 (COMMD6).	[12]

References

• [1] Prognosis and modulation mechanisms of COMMD6 in human tumours based on expression profiling and comprehensive bioinformatics analysis.Br J Cancer. 2019 Oct;121(8):699-709. doi: 10.1038/s41416-019-0571-x. Epub 2019 Sep 16.
• [2] COMMD9 promotes TFDP1/E2F1 transcriptional activity via interaction with TFDP1 in non-small cell lung cancer.Cell Signal. 2017 Jan;30:59-66. doi: 10.1016/j.cellsig.2016.11.016. Epub 2016 Nov 19.
• [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] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [6] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [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] In vitro and in vivo irinotecan-induced changes in expression profiles of cell cycle and apoptosis-associated genes in acute myeloid leukemia cells. Mol Cancer Ther. 2005 Jun;4(6):885-900.
• [9] 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.
• [10] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [11] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [12] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.