Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMXO4YB)

• DOT Name: Destrin (DSTN)
• Synonyms: Actin-depolymerizing factor; ADF
• Gene Name: DSTN
• Related Disease:
  Malaria
  Adult T-cell leukemia/lymphoma
  Advanced cancer
  Astrocytoma
  Autoimmune disease
  Colon cancer
  Colon carcinoma
  Colonic neoplasm
  Fragile X syndrome
  Lung cancer
  Lung carcinoma
  Melanoma
  Non-small-cell lung cancer
  Pancreatic cancer
  Prostate cancer
  Prostate carcinoma
  Sjogren syndrome
  Adult glioblastoma
  Charcot-Marie-Tooth disease type 3
  Glioblastoma multiforme
  Urinary bladder cancer
  Cardiac failure
  Chronic hepatitis B virus infection
  Congestive heart failure
  Glioma
• UniProt ID: DEST_HUMAN
• Pfam ID: PF00241
• Sequence:
  MASGVQVADEVCRIFYDMKVRKCSTPEEIKKRKKAVIFCLSADKKCIIVEEGKEILVGDV
  GVTITDPFKHFVGMLPEKDCRYALYDASFETKESRKEELMFFLWAPELAPLKSKMIYASS
  KDAIKKKFQGIKHECQANGPEDLNRACIAEKLGGSLIVAFEGCPV
• Function: Actin-depolymerizing protein. Severs actin filaments (F-actin) and binds to actin monomers (G-actin). Acts in a pH-independent manner.
• Tissue Specificity: Widely distributed in various tissues.

Molecular Interaction Atlas (MIA) of This DOT

25 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Malaria	DISQ9Y50	Definitive	Biomarker	[1]
Adult T-cell leukemia/lymphoma	DIS882XU	Strong	Altered Expression	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Astrocytoma	DISL3V18	Strong	Biomarker	[4]
Autoimmune disease	DISORMTM	Strong	Altered Expression	[5]
Colon cancer	DISVC52G	Strong	Altered Expression	[6]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[6]
Colonic neoplasm	DISSZ04P	Strong	Biomarker	[7]
Fragile X syndrome	DISE8W3A	Strong	Biomarker	[8]
Lung cancer	DISCM4YA	Strong	Biomarker	[9]
Lung carcinoma	DISTR26C	Strong	Biomarker	[9]
Melanoma	DIS1RRCY	Strong	Biomarker	[10]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[9]
Pancreatic cancer	DISJC981	Strong	Biomarker	[11]
Prostate cancer	DISF190Y	Strong	Genetic Variation	[12]
Prostate carcinoma	DISMJPLE	Strong	Genetic Variation	[12]
Sjogren syndrome	DISUBX7H	Strong	Altered Expression	[5]
Adult glioblastoma	DISVP4LU	moderate	Altered Expression	[13]
Charcot-Marie-Tooth disease type 3	DIS6DQK1	moderate	Biomarker	[14]
Glioblastoma multiforme	DISK8246	moderate	Altered Expression	[13]
Urinary bladder cancer	DISDV4T7	moderate	Biomarker	[15]
Cardiac failure	DISDC067	Limited	Biomarker	[16]
Chronic hepatitis B virus infection	DISHL4NT	Limited	Biomarker	[17]
Congestive heart failure	DIS32MEA	Limited	Biomarker	[16]
Glioma	DIS5RPEH	Limited	Altered Expression	[18]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Destrin (DSTN).	[19]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Destrin (DSTN).	[20]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Destrin (DSTN).	[21]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Destrin (DSTN).	[22]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Destrin (DSTN).	[23]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Destrin (DSTN).	[24]
Resveratrol	DM3RWXL	Phase 3	Resveratrol affects the expression of Destrin (DSTN).	[25]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Destrin (DSTN).	[28]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Destrin (DSTN).	[29]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Destrin (DSTN).	[30]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID increases the expression of Destrin (DSTN).	[31]
Okadaic acid	DM47CO1	Investigative	Okadaic acid decreases the expression of Destrin (DSTN).	[32]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Destrin (DSTN).	[26]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Destrin (DSTN).	[27]

References

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• [2] TCGF(IL 2)-receptor inducing factor(s). II. Possible role of ATL-derived factor (ADF) on constitutive IL 2 receptor expression of HTLV-I(+) T cell lines.J Immunol. 1985 Dec;135(6):3995-4003.
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• [16] A context-specific cardiac -catenin and GATA4 interaction influences TCF7L2 occupancy and remodels chromatin driving disease progression in the adult heart.Nucleic Acids Res. 2018 Apr 6;46(6):2850-2867. doi: 10.1093/nar/gky049.
• [17] Tenofovir disoproxil fumarate has a substantial efficacy against multidrug-resistant strains of hepatitis B virus.Liver Int. 2015 Oct;35(10):2265-74. doi: 10.1111/liv.12831. Epub 2015 Apr 17.
• [18] Interferon gamma up-regulates alpha 2 macroglobulin expression in human astrocytoma cells.J Neuroimmunol. 1994 Aug;53(1):31-7. doi: 10.1016/0165-5728(94)90061-2.
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• [23] 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.
• [24] 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.
• [25] Resveratrol downregulates Akt/GSK and ERK signalling pathways in OVCAR-3 ovarian cancer cells. Mol Biosyst. 2012 Apr;8(4):1078-87. doi: 10.1039/c2mb05486h. Epub 2012 Jan 10.
• [26] 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.
• [27] 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.
• [28] 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.
• [29] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
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• [31] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.
• [32] Proteomic analysis reveals multiple patterns of response in cells exposed to a toxin mixture. Chem Res Toxicol. 2009 Jun;22(6):1077-85.