Details of Drug Off-Target (DOT)

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

• DOT Name: Type II iodothyronine deiodinase (DIO2)
• Synonyms: EC 1.21.99.4; 5DII; DIOII; Type 2 DI; Type-II 5'-deiodinase
• Gene Name: DIO2
• Related Disease:
  Adult glioblastoma
  Glioblastoma multiforme
  Intellectual disability
  Myotonic dystrophy type 2
  Thyroid tumor
  Acute myocardial infarction
  Advanced cancer
  Alzheimer disease
  Autism spectrum disorder
  Autoimmune disease
  Bartsocas-Papas syndrome 1
  Bipolar disorder
  Brain neoplasm
  Cerebral infarction
  Colorectal carcinoma
  Coronary heart disease
  Depression
  Differentiated thyroid carcinoma
  Endometriosis
  Familial adenomatous polyposis
  Graves disease
  Hyperinsulinemia
  Hyperthyroidism
  Hypothyroidism
  Intestinal neoplasm
  Lipodystrophy
  Mesothelioma
  Osteoarthritis
  Polyp
  Prostate cancer
  Prostate carcinoma
  Pulmonary fibrosis
  Status epilepticus seizure
  Thyroid gland follicular carcinoma
  Arteriosclerosis
  Atherosclerosis
  Choriocarcinoma
  Non-insulin dependent diabetes
  Thyroid gland papillary carcinoma
  Cardiomyopathy
  Chronic obstructive pulmonary disease
  Goiter
  Hashimoto thyroiditis
  Pituitary tumor
  Rosacea
  Type-1/2 diabetes
• UniProt ID: IOD2_HUMAN
• EC Number: 1.21.99.4
• Pfam ID: PF00837
• Sequence:
  MGILSVDLLITLQILPVFFSNCLFLALYDSVILLKHVVLLLSRSKSTRGEWRRMLTSEGL
  RCVWKSFLLDAYKQVKLGEDAPNSSVVHVSSTEGGDNSGNGTQEKIAEGATCHLLDFASP
  ERPLVVNFGSATUPPFTSQLPAFRKLVEEFSSVADFLLVYIDEAHPSDGWAIPGDSSLSF
  EVKKHQNQEDRCAAAQQLLERFSLPPQCRVVADRMDNNANIAYGVAFERVCIVQRQKIAY
  LGGKGPFSYNLQEVRHWLEKNFSKRUKKTRLAG
• Function: Responsible for the deiodination of T4 (3,5,3',5'-tetraiodothyronine) into T3 (3,5,3'-triiodothyronine). Essential for providing the brain with appropriate levels of T3 during the critical period of development.
• Tissue Specificity: Isoform 1 is expressed in the lung, trachea, kidney, heart, skeletal muscle, placenta, fetal brain and several regions of the adult brain . Isoform 2 is expressed in the brain, heart, kidney and trachea .
• KEGG Pathway: Thyroid hormone sig.ling pathway (hsa04919)
• Reactome Pathway: Regulation of thyroid hormone activity (R-HSA-350864)
• BioCyc Pathway: MetaCyc:HS00008-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult glioblastoma	DISVP4LU	Definitive	Genetic Variation	[1]
Glioblastoma multiforme	DISK8246	Definitive	Genetic Variation	[1]
Intellectual disability	DISMBNXP	Definitive	Biomarker	[2]
Myotonic dystrophy type 2	DIS5ZWF1	Definitive	Genetic Variation	[3]
Thyroid tumor	DISLVKMD	Definitive	Altered Expression	[4]
Acute myocardial infarction	DISE3HTG	Strong	Genetic Variation	[5]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[6]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[7]
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[8]
Autoimmune disease	DISORMTM	Strong	Genetic Variation	[9]
Bartsocas-Papas syndrome 1	DIS12QS5	Strong	Altered Expression	[10]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[11]
Brain neoplasm	DISY3EKS	Strong	Altered Expression	[12]
Cerebral infarction	DISR1WNP	Strong	Biomarker	[13]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[6]
Coronary heart disease	DIS5OIP1	Strong	Genetic Variation	[5]
Depression	DIS3XJ69	Strong	Altered Expression	[14]
Differentiated thyroid carcinoma	DIS1V20Y	Strong	Genetic Variation	[15]
Endometriosis	DISX1AG8	Strong	Biomarker	[16]
Familial adenomatous polyposis	DISW53RE	Strong	Altered Expression	[6]
Graves disease	DISU4KOQ	Strong	Biomarker	[17]
Hyperinsulinemia	DISIDWT6	Strong	Genetic Variation	[18]
Hyperthyroidism	DISX87ZH	Strong	Altered Expression	[19]
Hypothyroidism	DISR0H6D	Strong	Biomarker	[20]
Intestinal neoplasm	DISK0GUH	Strong	Biomarker	[6]
Lipodystrophy	DIS3SGVD	Strong	Altered Expression	[21]
Mesothelioma	DISKWK9M	Strong	Biomarker	[22]
Osteoarthritis	DIS05URM	Strong	Genetic Variation	[23]
Polyp	DISRSLYF	Strong	Altered Expression	[6]
Prostate cancer	DISF190Y	Strong	Biomarker	[24]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[24]
Pulmonary fibrosis	DISQKVLA	Strong	Biomarker	[25]
Status epilepticus seizure	DISY3BIC	Strong	Biomarker	[26]
Thyroid gland follicular carcinoma	DISFK2QT	Strong	Altered Expression	[27]
Arteriosclerosis	DISK5QGC	moderate	Altered Expression	[28]
Atherosclerosis	DISMN9J3	moderate	Altered Expression	[28]
Choriocarcinoma	DISDBVNL	moderate	Biomarker	[29]
Non-insulin dependent diabetes	DISK1O5Z	moderate	Genetic Variation	[30]
Thyroid gland papillary carcinoma	DIS48YMM	moderate	Altered Expression	[31]
Cardiomyopathy	DISUPZRG	Limited	Genetic Variation	[32]
Chronic obstructive pulmonary disease	DISQCIRF	Limited	Biomarker	[33]
Goiter	DISLCGI6	Limited	Genetic Variation	[34]
Hashimoto thyroiditis	DIS77CDF	Limited	Genetic Variation	[35]
Pituitary tumor	DISN67JD	Limited	Altered Expression	[36]
Rosacea	DIS02PWG	Limited	Altered Expression	[37]
Type-1/2 diabetes	DISIUHAP	Limited	Genetic Variation	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
L-thyroxine	DM83HWL	Investigative	Type II iodothyronine deiodinase (DIO2) increases the metabolism of L-thyroxine.	[64]

3 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 Type II iodothyronine deiodinase (DIO2).	[38]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Type II iodothyronine deiodinase (DIO2).	[57]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Type II iodothyronine deiodinase (DIO2).	[59]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Type II iodothyronine deiodinase (DIO2).	[39]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Type II iodothyronine deiodinase (DIO2).	[40]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Type II iodothyronine deiodinase (DIO2).	[41]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Type II iodothyronine deiodinase (DIO2).	[42]
Quercetin	DM3NC4M	Approved	Quercetin increases the activity of Type II iodothyronine deiodinase (DIO2).	[43]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Type II iodothyronine deiodinase (DIO2).	[44]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Type II iodothyronine deiodinase (DIO2).	[45]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Type II iodothyronine deiodinase (DIO2).	[46]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Type II iodothyronine deiodinase (DIO2).	[47]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the activity of Type II iodothyronine deiodinase (DIO2).	[48]
Azacitidine	DMTA5OE	Approved	Azacitidine decreases the expression of Type II iodothyronine deiodinase (DIO2).	[49]
Mifepristone	DMGZQEF	Approved	Mifepristone increases the expression of Type II iodothyronine deiodinase (DIO2).	[50]
Alitretinoin	DMME8LH	Approved	Alitretinoin decreases the expression of Type II iodothyronine deiodinase (DIO2).	[39]
Pioglitazone	DMKJ485	Approved	Pioglitazone increases the activity of Type II iodothyronine deiodinase (DIO2).	[48]
Prednisolone	DMQ8FR2	Approved	Prednisolone increases the expression of Type II iodothyronine deiodinase (DIO2).	[51]
Methylprednisolone	DM4BDON	Approved	Methylprednisolone increases the expression of Type II iodothyronine deiodinase (DIO2).	[51]
Masoprocol	DMMVNZ0	Approved	Masoprocol decreases the activity of Type II iodothyronine deiodinase (DIO2).	[52]
Ergocalciferol	DMHO0AR	Approved	Ergocalciferol decreases the activity of Type II iodothyronine deiodinase (DIO2).	[52]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the activity of Type II iodothyronine deiodinase (DIO2).	[43]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Type II iodothyronine deiodinase (DIO2).	[53]
PEITC	DMOMN31	Phase 2	PEITC decreases the expression of Type II iodothyronine deiodinase (DIO2).	[54]
PF-02545920	DMJPE61	Phase 2	PF-02545920 increases the expression of Type II iodothyronine deiodinase (DIO2).	[56]
MG-132	DMKA2YS	Preclinical	MG-132 increases the expression of Type II iodothyronine deiodinase (DIO2).	[58]
Ciglitazone	DMAPO0T	Preclinical	Ciglitazone increases the activity of Type II iodothyronine deiodinase (DIO2).	[48]
SSR-69071	DMWL4MI	Terminated	SSR-69071 decreases the activity of Type II iodothyronine deiodinase (DIO2).	[52]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Type II iodothyronine deiodinase (DIO2).	[60]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Type II iodothyronine deiodinase (DIO2).	[61]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Type II iodothyronine deiodinase (DIO2).	[62]
Cycloheximide	DMGDA3C	Investigative	Cycloheximide decreases the activity of Type II iodothyronine deiodinase (DIO2).	[22]
Kaempferol	DMHEMUB	Investigative	Kaempferol increases the expression of Type II iodothyronine deiodinase (DIO2).	[43]
GW7647	DM9RD0C	Investigative	GW7647 increases the activity of Type II iodothyronine deiodinase (DIO2).	[48]
3,7,3',4'-TETRAHYDROXYFLAVONE	DMES906	Investigative	3,7,3',4'-TETRAHYDROXYFLAVONE increases the activity of Type II iodothyronine deiodinase (DIO2).	[43]
Linoleic acid	DMDGPY9	Investigative	Linoleic acid decreases the activity of Type II iodothyronine deiodinase (DIO2).	[52]
Piceatannol	DMYOP45	Investigative	Piceatannol decreases the activity of Type II iodothyronine deiodinase (DIO2).	[43]
Alpha-linolenic acid	DMY64HE	Investigative	Alpha-linolenic acid decreases the activity of Type II iodothyronine deiodinase (DIO2).	[52]
BUTEIN	DM8E54P	Investigative	BUTEIN decreases the activity of Type II iodothyronine deiodinase (DIO2).	[43]
BADGE	DMCK5DG	Investigative	BADGE decreases the activity of Type II iodothyronine deiodinase (DIO2).	[52]
2,3-dichloro-1,4-naphthoquinone	DMPCGSD	Investigative	2,3-dichloro-1,4-naphthoquinone decreases the activity of Type II iodothyronine deiodinase (DIO2).	[52]
Triiodo-l-thyronine	DMVJD1A	Investigative	Triiodo-l-thyronine decreases the activity of Type II iodothyronine deiodinase (DIO2).	[58]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
ANW-32821	DMMJOZD	Phase 2	ANW-32821 increases the degradation of Type II iodothyronine deiodinase (DIO2).	[55]

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