Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3AWE8O)

• DOT Name: LIM and cysteine-rich domains protein 1 (LMCD1)
• Synonyms: Dyxin
• Gene Name: LMCD1
• Related Disease:
  Hepatocellular carcinoma
  Metastatic malignant neoplasm
  Myopathy
  Mitral valve prolapse
  Prostate cancer
  Prostate carcinoma
• UniProt ID: LMCD1_HUMAN
• Pfam ID: PF00412 ; PF06297
• Sequence:
  MAKVAKDLNPGVKKMSLGQLQSARGVACLGCKGTCSGFEPHSWRKICKSCKCSQEDHCLT
  SDLEDDRKIGRLLMDSKYSTLTARVKGGDGIRIYKRNRMIMTNPIATGKDPTFDTITYEW
  APPGVTQKLGLQYMELIPKEKQPVTGTEGAFYRRRQLMHQLPIYDQDPSRCRGLLENELK
  LMEEFVKQYKSEALGVGEVALPGQGGLPKEEGKQQEKPEGAETTAATTNGSLSDPSKEVE
  YVCELCKGAAPPDSPVVYSDRAGYNKQWHPTCFVCAKCSEPLVDLIYFWKDGAPWCGRHY
  CESLRPRCSGCDEIIFAEDYQRVEDLAWHRKHFVCEGCEQLLSGRAYIVTKGQLLCPTCS
  KSKRS
• Function: Transcriptional cofactor that restricts GATA6 function by inhibiting DNA-binding, resulting in repression of GATA6 transcriptional activation of downstream target genes. Represses GATA6-mediated trans activation of lung- and cardiac tissue-specific promoters. Inhibits DNA-binding by GATA4 and GATA1 to the cTNC promoter. Plays a critical role in the development of cardiac hypertrophy via activation of calcineurin/nuclear factor of activated T-cells signaling pathway.
• Tissue Specificity: Expressed in the heart (at protein level). Expressed in many tissues with highest abundance in skeletal muscle.
• Reactome Pathway: Surfactant metabolism (R-HSA-5683826)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Strong	Genetic Variation	[1]
Metastatic malignant neoplasm	DIS86UK6	Strong	Genetic Variation	[1]
Myopathy	DISOWG27	Strong	Altered Expression	[2]
Mitral valve prolapse	DISNCHQ3	moderate	Biomarker	[3]
Prostate cancer	DISF190Y	Limited	Biomarker	[4]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of LIM and cysteine-rich domains protein 1 (LMCD1).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of LIM and cysteine-rich domains protein 1 (LMCD1).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of LIM and cysteine-rich domains protein 1 (LMCD1).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of LIM and cysteine-rich domains protein 1 (LMCD1).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of LIM and cysteine-rich domains protein 1 (LMCD1).	[9]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of LIM and cysteine-rich domains protein 1 (LMCD1).	[10]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of LIM and cysteine-rich domains protein 1 (LMCD1).	[11]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of LIM and cysteine-rich domains protein 1 (LMCD1).	[12]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of LIM and cysteine-rich domains protein 1 (LMCD1).	[13]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of LIM and cysteine-rich domains protein 1 (LMCD1).	[14]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of LIM and cysteine-rich domains protein 1 (LMCD1).	[15]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of LIM and cysteine-rich domains protein 1 (LMCD1).	[16]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of LIM and cysteine-rich domains protein 1 (LMCD1).	[17]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of LIM and cysteine-rich domains protein 1 (LMCD1).	[18]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of LIM and cysteine-rich domains protein 1 (LMCD1).	[19]
Menadione	DMSJDTY	Approved	Menadione affects the expression of LIM and cysteine-rich domains protein 1 (LMCD1).	[20]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of LIM and cysteine-rich domains protein 1 (LMCD1).	[21]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of LIM and cysteine-rich domains protein 1 (LMCD1).	[22]
Cidofovir	DMA13GD	Approved	Cidofovir increases the expression of LIM and cysteine-rich domains protein 1 (LMCD1).	[6]
Mifepristone	DMGZQEF	Approved	Mifepristone decreases the expression of LIM and cysteine-rich domains protein 1 (LMCD1).	[23]
Ifosfamide	DMCT3I8	Approved	Ifosfamide decreases the expression of LIM and cysteine-rich domains protein 1 (LMCD1).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of LIM and cysteine-rich domains protein 1 (LMCD1).	[24]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of LIM and cysteine-rich domains protein 1 (LMCD1).	[25]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of LIM and cysteine-rich domains protein 1 (LMCD1).	[26]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of LIM and cysteine-rich domains protein 1 (LMCD1).	[27]
cinnamaldehyde	DMZDUXG	Investigative	cinnamaldehyde decreases the expression of LIM and cysteine-rich domains protein 1 (LMCD1).	[28]

References

• [1] Somatic LMCD1 mutations promoted cell migration and tumor metastasis in hepatocellular carcinoma.Oncogene. 2012 May 24;31(21):2640-52. doi: 10.1038/onc.2011.440. Epub 2011 Sep 26.
• [2] LIM and cysteine-rich domains 1 (LMCD1) regulates skeletal muscle hypertrophy, calcium handling, and force.Skelet Muscle. 2019 Oct 31;9(1):26. doi: 10.1186/s13395-019-0214-1.
• [3] Genetic association analyses highlight biological pathways underlying mitral valve prolapse.Nat Genet. 2015 Oct;47(10):1206-11. doi: 10.1038/ng.3383. Epub 2015 Aug 24.
• [4] Identification of Novel Epigenetic Markers of Prostate Cancer by NotI-Microarray Analysis.Dis Markers. 2015;2015:241301. doi: 10.1155/2015/241301. Epub 2015 Sep 28.
• [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] Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
• [7] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [10] 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.
• [11] 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.
• [12] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [13] 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.
• [14] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [15] Gene microarray analysis of human renal cell carcinoma: the effects of HDAC inhibition and retinoid treatment. Cancer Biol Ther. 2008 Oct;7(10):1607-18.
• [16] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [17] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [18] 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.
• [19] Progesterone regulation of implantation-related genes: new insights into the role of oestrogen. Cell Mol Life Sci. 2007 Apr;64(7-8):1009-32.
• [20] 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.
• [21] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [22] Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
• [23] Mifepristone induced progesterone withdrawal reveals novel regulatory pathways in human endometrium. Mol Hum Reprod. 2007 Sep;13(9):641-54.
• [24] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [25] 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.
• [26] 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.
• [27] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [28] Comparative DNA microarray analysis of human monocyte derived dendritic cells and MUTZ-3 cells exposed to the moderate skin sensitizer cinnamaldehyde. Toxicol Appl Pharmacol. 2009 Sep 15;239(3):273-83.