Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT84YKPM)

• DOT Name: Myosin light polypeptide 6 (MYL6)
• Synonyms: 17 kDa myosin light chain; LC17; Myosin light chain 3; MLC-3; Myosin light chain alkali 3; Myosin light chain A3; Smooth muscle and nonmuscle myosin light chain alkali 6
• Gene Name: MYL6
• UniProt ID: MYL6_HUMAN
• Sequence:
  MCDFTEDQTAEFKEAFQLFDRTGDGKILYSQCGDVMRALGQNPTNAEVLKVLGNPKSDEM
  NVKVLDFEHFLPMLQTVAKNKDQGTYEDYVEGLRVFDKEGNGTVMGAEIRHVLVTLGEKM
  TEEEVEMLVAGHEDSNGCINYEAFVRHILSG
• Function: Regulatory light chain of myosin. Does not bind calcium.
• KEGG Pathway:
  Vascular smooth muscle contraction (hsa04270)
  Tight junction (hsa04530)
  Motor proteins (hsa04814)
  Oxytocin sig.ling pathway (hsa04921)
• Reactome Pathway:
  Sema4D induced cell migration and growth-cone collapse (R-HSA-416572)
  Smooth Muscle Contraction (R-HSA-445355)
  RHO GTPases activate PKNs (R-HSA-5625740)
  RHO GTPases activate CIT (R-HSA-5625900)
  RHO GTPases Activate ROCKs (R-HSA-5627117)
  RHO GTPases activate PAKs (R-HSA-5627123)
  EPHA-mediated growth cone collapse (R-HSA-3928663)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
PEITC	DMOMN31	Phase 2	Myosin light polypeptide 6 (MYL6) affects the binding of PEITC.	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Myosin light polypeptide 6 (MYL6).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Myosin light polypeptide 6 (MYL6).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Myosin light polypeptide 6 (MYL6).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Myosin light polypeptide 6 (MYL6).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Myosin light polypeptide 6 (MYL6).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Myosin light polypeptide 6 (MYL6).	[6]
Selenium	DM25CGV	Approved	Selenium increases the expression of Myosin light polypeptide 6 (MYL6).	[7]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Myosin light polypeptide 6 (MYL6).	[8]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Myosin light polypeptide 6 (MYL6).	[9]
Nicotine	DMWX5CO	Approved	Nicotine decreases the expression of Myosin light polypeptide 6 (MYL6).	[10]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Myosin light polypeptide 6 (MYL6).	[11]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Myosin light polypeptide 6 (MYL6).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Myosin light polypeptide 6 (MYL6).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Myosin light polypeptide 6 (MYL6).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Myosin light polypeptide 6 (MYL6).	[15]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Myosin light polypeptide 6 (MYL6).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Myosin light polypeptide 6 (MYL6).	[13]

References

• [1] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [2] Pharmacogenomic analysis of acute promyelocytic leukemia cells highlights CYP26 cytochrome metabolism in differential all-trans retinoic acid sensitivity. Blood. 2007 May 15;109(10):4450-60.
• [3] 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.
• [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] 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] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [8] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [9] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [10] Nicotinic modulation of gene expression in SH-SY5Y neuroblastoma cells. Brain Res. 2006 Oct 20;1116(1):39-49.
• [11] Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein. Mol Cell Proteomics. 2011 Jan;10(1):M110.002170.
• [12] Proteomic analysis of MCF-7 cells treated with benzo[a]pyrene, dibenzo[a,l]pyrene, coal tar extract, and diesel exhaust extract. Toxicology. 2008 Jul 10;249(1):1-10.
• [13] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [14] 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.
• [15] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [16] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [17] Identification of potential protein targets of isothiocyanates by proteomics. Chem Res Toxicol. 2011 Oct 17;24(10):1735-43. doi: 10.1021/tx2002806. Epub 2011 Aug 26.