Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVCZ7HI)

• DOT Name: Metallothionein-3 (MT3)
• Synonyms: MT-3; GIFB; GIF; Growth inhibitory factor; Metallothionein-III; MT-III
• Gene Name: MT3
• Related Disease:
  Acute myelogenous leukaemia
  Adenoma
  Adrenocortical carcinoma
  Advanced cancer
  Alzheimer disease
  Amyloidosis
  Bowel dysfunction
  Breast cancer
  Breast carcinoma
  Breast disorder
  Breast neoplasm
  Carcinoma of esophagus
  Creutzfeldt Jacob disease
  Depression
  Dilated cardiomyopathy 1A
  Esophageal cancer
  Esophageal squamous cell carcinoma
  Glioblastoma multiforme
  Hereditary intrinsic factor deficiency
  Hypothyroidism
  Imerslund-Grasbeck syndrome
  Intestinal disorder
  Motor neurone disease
  Neoplasm of esophagus
  Non-small-cell lung cancer
  Parkinson disease
  Polycythemia
  Primary aldosteronism
  Prostate neoplasm
  Scleroderma
  Squamous cell carcinoma
  Stomach cancer
  Systemic sclerosis
  Pernicious anemia
  Adenocarcinoma
  Adult respiratory distress syndrome
  Anxiety
  Anxiety disorder
  Bladder disease
  Kaposi sarcoma
  Lung cancer
  Lung carcinoma
  Neuroblastoma
• UniProt ID: MT3_HUMAN
• PDB ID: 2F5H; 2FJ4; 2FJ5
• Pfam ID: PF00131
• Sequence:
  MDPETCPCPSGGSCTCADSCKCEGCKCTSCKKSCCSCCPAECEKCAKDCVCKGGEAAEAE
  AEKCSCCQ
• Function: Binds heavy metals. Contains three zinc and three copper atoms per polypeptide chain and only a negligible amount of cadmium. Inhibits survival and neurite formation of cortical neurons in vitro.
• Tissue Specificity: Abundant in a subset of astrocytes in the normal human brain, but greatly reduced in the Alzheimer disease (AD) brain.
• Reactome Pathway: Metallothioneins bind metals (R-HSA-5661231)

Molecular Interaction Atlas (MIA) of This DOT

43 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Strong	Posttranslational Modification	[1]
Adenoma	DIS78ZEV	Strong	Biomarker	[2]
Adrenocortical carcinoma	DISZF4HX	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[3]
Alzheimer disease	DISF8S70	Strong	Biomarker	[4]
Amyloidosis	DISHTAI2	Strong	Biomarker	[5]
Bowel dysfunction	DISL9FWR	Strong	Altered Expression	[6]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[7]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[8]
Breast disorder	DISJTGMA	Strong	Biomarker	[9]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[8]
Carcinoma of esophagus	DISS6G4D	Strong	Altered Expression	[10]
Creutzfeldt Jacob disease	DISCB6RX	Strong	Biomarker	[11]
Depression	DIS3XJ69	Strong	Altered Expression	[12]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Biomarker	[9]
Esophageal cancer	DISGB2VN	Strong	Altered Expression	[10]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Posttranslational Modification	[13]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[14]
Hereditary intrinsic factor deficiency	DISCZQBU	Strong	Genetic Variation	[15]
Hypothyroidism	DISR0H6D	Strong	Biomarker	[16]
Imerslund-Grasbeck syndrome	DISQ84S1	Strong	Genetic Variation	[17]
Intestinal disorder	DISGPMUQ	Strong	Altered Expression	[6]
Motor neurone disease	DISUHWUI	Strong	Biomarker	[18]
Neoplasm of esophagus	DISOLKAQ	Strong	Altered Expression	[10]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[19]
Parkinson disease	DISQVHKL	Strong	Biomarker	[20]
Polycythemia	DIS8B6VW	Strong	Biomarker	[21]
Primary aldosteronism	DISOEFNH	Strong	Biomarker	[2]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[22]
Scleroderma	DISVQ342	Strong	Biomarker	[23]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[13]
Stomach cancer	DISKIJSX	Strong	Posttranslational Modification	[24]
Systemic sclerosis	DISF44L6	Strong	Biomarker	[23]
Pernicious anemia	DISWV404	moderate	Genetic Variation	[15]
Adenocarcinoma	DIS3IHTY	Limited	Posttranslational Modification	[25]
Adult respiratory distress syndrome	DISIJV47	Limited	Biomarker	[26]
Anxiety	DISIJDBA	Limited	Biomarker	[27]
Anxiety disorder	DISBI2BT	Limited	Biomarker	[27]
Bladder disease	DISTVIQI	Limited	Altered Expression	[28]
Kaposi sarcoma	DISC1H1Z	Limited	Biomarker	[29]
Lung cancer	DISCM4YA	Limited	Biomarker	[30]
Lung carcinoma	DISTR26C	Limited	Biomarker	[30]
Neuroblastoma	DISVZBI4	Limited	Altered Expression	[31]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Metallothionein-3 (MT3) decreases the response to substance of Doxorubicin.	[43]
Hydrogen peroxide	DM1NG5W	Approved	Metallothionein-3 (MT3) decreases the response to substance of Hydrogen peroxide.	[50]

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
8-hydroxyguanine	DMT9BPN	Investigative	Metallothionein-3 (MT3) decreases the abundance of 8-hydroxyguanine.	[51]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Metallothionein-3 (MT3).	[32]
Tretinoin	DM49DUI	Approved	Tretinoin affects the expression of Metallothionein-3 (MT3).	[33]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Metallothionein-3 (MT3).	[34]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Metallothionein-3 (MT3).	[35]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Metallothionein-3 (MT3).	[36]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Metallothionein-3 (MT3).	[37]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Metallothionein-3 (MT3).	[38]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Metallothionein-3 (MT3).	[8]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Metallothionein-3 (MT3).	[40]
Gallium nitrate	DMF9O6B	Approved	Gallium nitrate increases the expression of Metallothionein-3 (MT3).	[41]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Metallothionein-3 (MT3).	[8]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of Metallothionein-3 (MT3).	[33]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Metallothionein-3 (MT3).	[44]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Metallothionein-3 (MT3).	[46]
D-glucose	DMMG2TO	Investigative	D-glucose decreases the expression of Metallothionein-3 (MT3).	[47]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Metallothionein-3 (MT3).	[35]

3 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 Metallothionein-3 (MT3).	[42]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Metallothionein-3 (MT3).	[45]
Edetic acid	DM10D85	Investigative	Edetic acid increases the alkylation of Metallothionein-3 (MT3).	[48]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
LY294002	DMY1AFS	Phase 1	LY294002 decreases the response to substance of Metallothionein-3 (MT3).	[43]
Wortmannin	DM8EVK5	Terminated	Wortmannin decreases the response to substance of Metallothionein-3 (MT3).	[43]

References

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