Details of Drug Off-Target (DOT)

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

• DOT Name: Calponin-3 (CNN3)
• Synonyms: Calponin, acidic isoform
• Gene Name: CNN3
• Related Disease:
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Epilepsy
  Gastric cancer
  Multiple sclerosis
  Myositis disease
  Neoplasm
  Prostate cancer
  Prostate neoplasm
  Sjogren syndrome
  Stomach cancer
  Systemic lupus erythematosus
  MALT lymphoma
  Carcinoma
  Undifferentiated carcinoma
• UniProt ID: CNN3_HUMAN
• Pfam ID: PF00402 ; PF00307
• Sequence:
  MTHFNKGPSYGLSAEVKNKIASKYDHQAEEDLRNWIEEVTGMSIGPNFQLGLKDGIILCE
  LINKLQPGSVKKVNESSLNWPQLENIGNFIKAIQAYGMKPHDIFEANDLFENGNMTQVQT
  TLVALAGLAKTKGFHTTIDIGVKYAEKQTRRFDEGKLKAGQSVIGLQMGTNKCASQAGMT
  AYGTRRHLYDPKMQTDKPFDQTTISLQMGTNKGASQAGMLAPGTRRDIYDQKLTLQPVDN
  STISLQMGTNKVASQKGMSVYGLGRQVYDPKYCAAPTEPVIHNGSQGTGTNGSEISDSDY
  QAEYPDEYHGEYQDDYPRDYQYSDQGIDY
• Function: Thin filament-associated protein that is implicated in the regulation and modulation of smooth muscle contraction. It is capable of binding to actin, calmodulin and tropomyosin. The interaction of calponin with actin inhibits the actomyosin Mg-ATPase activity.
• Tissue Specificity: Expressed in both non-smooth muscle tissues as well as smooth muscle tissues.

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colon cancer	DISVC52G	Strong	Altered Expression	[1]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[2]
Epilepsy	DISBB28L	Strong	Biomarker	[3]
Gastric cancer	DISXGOUK	Strong	Biomarker	[4]
Multiple sclerosis	DISB2WZI	Strong	Biomarker	[5]
Myositis disease	DISCIXF0	Strong	Biomarker	[5]
Neoplasm	DISZKGEW	Strong	Biomarker	[6]
Prostate cancer	DISF190Y	Strong	Biomarker	[7]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[7]
Sjogren syndrome	DISUBX7H	Strong	Biomarker	[5]
Stomach cancer	DISKIJSX	Strong	Biomarker	[4]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[5]
MALT lymphoma	DIS1AVVE	moderate	Genetic Variation	[8]
Carcinoma	DISH9F1N	Limited	Biomarker	[9]
Undifferentiated carcinoma	DISIAZST	Limited	Biomarker	[9]

4 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 Calponin-3 (CNN3).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Calponin-3 (CNN3).	[22]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Calponin-3 (CNN3).	[24]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Calponin-3 (CNN3).	[26]

14 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 Calponin-3 (CNN3).	[11]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Calponin-3 (CNN3).	[12]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Calponin-3 (CNN3).	[13]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Calponin-3 (CNN3).	[14]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Calponin-3 (CNN3).	[15]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Calponin-3 (CNN3).	[16]
Selenium	DM25CGV	Approved	Selenium increases the expression of Calponin-3 (CNN3).	[17]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Calponin-3 (CNN3).	[18]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of Calponin-3 (CNN3).	[19]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Calponin-3 (CNN3).	[20]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Calponin-3 (CNN3).	[23]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Calponin-3 (CNN3).	[25]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Calponin-3 (CNN3).	[27]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Calponin-3 (CNN3).	[28]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of Calponin-3 (CNN3).	[21]

References

• [1] Calponin 3 promotes invasion and drug resistance of colon cancer cells.World J Gastrointest Oncol. 2019 Nov 15;11(11):971-982. doi: 10.4251/wjgo.v11.i11.971.
• [2] Establishment and Characterization of Paired Primary and Peritoneal Seeding Human Colorectal Cancer Cell Lines: Identification of Genes That Mediate Metastatic Potential.Transl Oncol. 2018 Oct;11(5):1232-1243. doi: 10.1016/j.tranon.2018.07.014. Epub 2018 Aug 14.
• [3] Increased expression of calponin-3 in epileptic patients and experimental rats.Exp Neurol. 2012 Jan;233(1):430-7. doi: 10.1016/j.expneurol.2011.11.014. Epub 2011 Nov 15.
• [4] Calponin 3 Regulates Cell Invasion and Doxorubicin Resistance in Gastric Cancer.Gastroenterol Res Pract. 2019 Feb 18;2019:3024970. doi: 10.1155/2019/3024970. eCollection 2019.
• [5] Brief Report: Anti-Calponin 3 Autoantibodies: A Newly Identified Specificity in Patients With Sjgren's Syndrome.Arthritis Rheumatol. 2018 Oct;70(10):1610-1616. doi: 10.1002/art.40550. Epub 2018 Sep 3.
• [6] Multi-dimensional immunoproteomics coupled with in vitro recapitulation of oncogenic NRAS(Q61R) identifies diagnostically relevant autoantibody biomarkers in thyroid neoplasia.Cancer Lett. 2019 Dec 28;467:96-106. doi: 10.1016/j.canlet.2019.07.013. Epub 2019 Jul 18.
• [7] Identification of genes potentially involved in the acquisition of androgen-independent and metastatic tumor growth in an autochthonous genetically engineered mouse prostate cancer model.Prostate. 2007 Jan 1;67(1):83-106. doi: 10.1002/pros.20505.
• [8] Mucosa-associated lymphoid tissue lymphoma: novel translocations including rearrangements of ODZ2, JMJD2C, and CNN3.Clin Cancer Res. 2008 Oct 15;14(20):6426-31. doi: 10.1158/1078-0432.CCR-08-0702.
• [9] cDNA microarray profiling of rat mammary gland carcinomas induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and 7,12-dimethylbenz[a]anthracene.Carcinogenesis. 2002 Oct;23(10):1561-8. doi: 10.1093/carcin/23.10.1561.
• [10] 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.
• [11] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [12] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [13] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [14] 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.
• [15] 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.
• [16] 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.
• [17] 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.
• [18] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [19] Effects of acute ethanol treatment on NCCIT cells and NCCIT cell-derived embryoid bodies (EBs). Toxicol In Vitro. 2010 Sep;24(6):1696-704. doi: 10.1016/j.tiv.2010.05.017. Epub 2010 May 26.
• [20] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
• [21] Proteomic analysis of the cellular response to a potent sensitiser unveils the dynamics of haptenation in living cells. Toxicology. 2020 Dec 1;445:152603. doi: 10.1016/j.tox.2020.152603. Epub 2020 Sep 28.
• [22] 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.
• [23] 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.
• [24] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [25] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [26] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [27] 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.
• [28] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.