Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUULW5Z)

• DOT Name: DNA-binding protein inhibitor ID-3 (ID3)
• Synonyms: Class B basic helix-loop-helix protein 25; bHLHb25; Helix-loop-helix protein HEIR-1; ID-like protein inhibitor HLH 1R21; Inhibitor of DNA binding 3; Inhibitor of differentiation 3
• Gene Name: ID3
• Related Disease:
  Acute erythroid leukemia
  Adenocarcinoma
  Arteriosclerosis
  Atherosclerosis
  B-cell lymphoma
  B-cell neoplasm
  Burkitt lymphoma
  Cholangiocarcinoma
  Chromosomal disorder
  Colon cancer
  Colonic neoplasm
  Intrahepatic cholangiocarcinoma
  Lung cancer
  Lung neoplasm
  Lymphoma
  Metastatic malignant neoplasm
  Myocardial ischemia
  Neoplasm
  Nervous system disease
  Neuroblastoma
  Sjogren syndrome
  T-cell lymphoma
  Thyroid cancer
  Thyroid gland carcinoma
  Thyroid tumor
  Advanced cancer
  Lung adenocarcinoma
  Metabolic disorder
  Obesity
  Prostate carcinoma
  Type-1 diabetes
  Gastric neoplasm
  Carcinoma
  Prostate cancer
  Prostate neoplasm
  Rett syndrome
  Undifferentiated carcinoma
• UniProt ID: ID3_HUMAN
• PDB ID: 2LFH
• Pfam ID: PF00010
• Sequence:
  MKALSPVRGCYEAVCCLSERSLAIARGRGKGPAAEEPLSLLDDMNHCYSRLRELVPGVPR
  GTQLSQVEILQRVIDYILDLQVVLAEPAPGPPDGPHLPIQTAELTPELVISNDKRSFCH
• Function: Transcriptional regulator (lacking a basic DNA binding domain) which negatively regulates the basic helix-loop-helix (bHLH) transcription factors by forming heterodimers and inhibiting their DNA binding and transcriptional activity. Implicated in regulating a variety of cellular processes, including cellular growth, senescence, differentiation, apoptosis, angiogenesis, and neoplastic transformation. Involved in myogenesis by inhibiting skeletal muscle and cardiac myocyte differentiation and promoting muscle precursor cells proliferation. Inhibits the binding of E2A-containing protein complexes to muscle creatine kinase E-box enhancer. Regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-BMAL1 heterodimer.
• Tissue Specificity: Expressed abundantly in lung, kidney and adrenal gland, but not in adult brain.
• KEGG Pathway:
  TGF-beta sig.ling pathway (hsa04350)
  Sig.ling pathways regulating pluripotency of stem cells (hsa04550)
• Reactome Pathway: NGF-stimulated transcription (R-HSA-9031628)

Molecular Interaction Atlas (MIA) of This DOT

37 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute erythroid leukemia	DISZFC1O	Strong	Altered Expression	[1]
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[2]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[3]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[3]
B-cell lymphoma	DISIH1YQ	Strong	Altered Expression	[4]
B-cell neoplasm	DISVY326	Strong	Altered Expression	[5]
Burkitt lymphoma	DIS9D5XU	Strong	Altered Expression	[4]
Cholangiocarcinoma	DIS71F6X	Strong	Altered Expression	[6]
Chromosomal disorder	DISM5BB5	Strong	Genetic Variation	[7]
Colon cancer	DISVC52G	Strong	Biomarker	[8]
Colonic neoplasm	DISSZ04P	Strong	Biomarker	[8]
Intrahepatic cholangiocarcinoma	DIS6GOC8	Strong	Biomarker	[6]
Lung cancer	DISCM4YA	Strong	Biomarker	[2]
Lung neoplasm	DISVARNB	Strong	Biomarker	[2]
Lymphoma	DISN6V4S	Strong	Genetic Variation	[7]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[9]
Myocardial ischemia	DISFTVXF	Strong	Biomarker	[10]
Neoplasm	DISZKGEW	Strong	Biomarker	[11]
Nervous system disease	DISJ7GGT	Strong	Biomarker	[12]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[13]
Sjogren syndrome	DISUBX7H	Strong	Biomarker	[14]
T-cell lymphoma	DISSXRTQ	Strong	Genetic Variation	[15]
Thyroid cancer	DIS3VLDH	Strong	Altered Expression	[16]
Thyroid gland carcinoma	DISMNGZ0	Strong	Altered Expression	[16]
Thyroid tumor	DISLVKMD	Strong	Altered Expression	[16]
Advanced cancer	DISAT1Z9	moderate	Altered Expression	[6]
Lung adenocarcinoma	DISD51WR	moderate	Biomarker	[5]
Metabolic disorder	DIS71G5H	moderate	Biomarker	[17]
Obesity	DIS47Y1K	moderate	Biomarker	[17]
Prostate carcinoma	DISMJPLE	moderate	Altered Expression	[18]
Type-1 diabetes	DIS7HLUB	moderate	Genetic Variation	[19]
Gastric neoplasm	DISOKN4Y	Disputed	Biomarker	[20]
Carcinoma	DISH9F1N	Limited	Biomarker	[21]
Prostate cancer	DISF190Y	Limited	Altered Expression	[18]
Prostate neoplasm	DISHDKGQ	Limited	Biomarker	[22]
Rett syndrome	DISGG5UV	Limited	Biomarker	[23]
Undifferentiated carcinoma	DISIAZST	Limited	Biomarker	[21]

55 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 DNA-binding protein inhibitor ID-3 (ID3).	[24]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of DNA-binding protein inhibitor ID-3 (ID3).	[25]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of DNA-binding protein inhibitor ID-3 (ID3).	[26]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of DNA-binding protein inhibitor ID-3 (ID3).	[27]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of DNA-binding protein inhibitor ID-3 (ID3).	[28]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of DNA-binding protein inhibitor ID-3 (ID3).	[29]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of DNA-binding protein inhibitor ID-3 (ID3).	[30]
Quercetin	DM3NC4M	Approved	Quercetin affects the expression of DNA-binding protein inhibitor ID-3 (ID3).	[25]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of DNA-binding protein inhibitor ID-3 (ID3).	[31]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of DNA-binding protein inhibitor ID-3 (ID3).	[32]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of DNA-binding protein inhibitor ID-3 (ID3).	[33]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of DNA-binding protein inhibitor ID-3 (ID3).	[34]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of DNA-binding protein inhibitor ID-3 (ID3).	[35]
Marinol	DM70IK5	Approved	Marinol decreases the expression of DNA-binding protein inhibitor ID-3 (ID3).	[36]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of DNA-binding protein inhibitor ID-3 (ID3).	[37]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of DNA-binding protein inhibitor ID-3 (ID3).	[38]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of DNA-binding protein inhibitor ID-3 (ID3).	[39]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of DNA-binding protein inhibitor ID-3 (ID3).	[27]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the expression of DNA-binding protein inhibitor ID-3 (ID3).	[40]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of DNA-binding protein inhibitor ID-3 (ID3).	[41]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of DNA-binding protein inhibitor ID-3 (ID3).	[42]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of DNA-binding protein inhibitor ID-3 (ID3).	[43]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of DNA-binding protein inhibitor ID-3 (ID3).	[40]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of DNA-binding protein inhibitor ID-3 (ID3).	[44]
Azacitidine	DMTA5OE	Approved	Azacitidine increases the expression of DNA-binding protein inhibitor ID-3 (ID3).	[35]
Colchicine	DM2POTE	Approved	Colchicine decreases the expression of DNA-binding protein inhibitor ID-3 (ID3).	[29]
Prednisolone	DMQ8FR2	Approved	Prednisolone increases the expression of DNA-binding protein inhibitor ID-3 (ID3).	[44]
Methylprednisolone	DM4BDON	Approved	Methylprednisolone increases the expression of DNA-binding protein inhibitor ID-3 (ID3).	[44]
Estrone	DM5T6US	Approved	Estrone decreases the expression of DNA-binding protein inhibitor ID-3 (ID3).	[40]
Adenine	DMZLHKJ	Approved	Adenine decreases the expression of DNA-binding protein inhibitor ID-3 (ID3).	[29]
Mestranol	DMG3F94	Approved	Mestranol decreases the expression of DNA-binding protein inhibitor ID-3 (ID3).	[40]
Methimazole	DM25FL8	Approved	Methimazole increases the expression of DNA-binding protein inhibitor ID-3 (ID3).	[45]
Pantothenic acid	DM091H2	Approved	Pantothenic acid increases the expression of DNA-binding protein inhibitor ID-3 (ID3).	[46]
Propylthiouracil	DM6D7N8	Approved	Propylthiouracil increases the expression of DNA-binding protein inhibitor ID-3 (ID3).	[45]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of DNA-binding protein inhibitor ID-3 (ID3).	[47]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of DNA-binding protein inhibitor ID-3 (ID3).	[48]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of DNA-binding protein inhibitor ID-3 (ID3).	[49]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of DNA-binding protein inhibitor ID-3 (ID3).	[30]
Phenol	DM1QSM3	Phase 2/3	Phenol increases the expression of DNA-binding protein inhibitor ID-3 (ID3).	[50]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of DNA-binding protein inhibitor ID-3 (ID3).	[51]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of DNA-binding protein inhibitor ID-3 (ID3).	[52]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of DNA-binding protein inhibitor ID-3 (ID3).	[54]
HEXESTROL	DM9AGWQ	Withdrawn from market	HEXESTROL decreases the expression of DNA-binding protein inhibitor ID-3 (ID3).	[40]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of DNA-binding protein inhibitor ID-3 (ID3).	[55]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of DNA-binding protein inhibitor ID-3 (ID3).	[57]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of DNA-binding protein inhibitor ID-3 (ID3).	[58]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of DNA-binding protein inhibitor ID-3 (ID3).	[59]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of DNA-binding protein inhibitor ID-3 (ID3).	[60]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of DNA-binding protein inhibitor ID-3 (ID3).	[61]
geraniol	DMS3CBD	Investigative	geraniol increases the expression of DNA-binding protein inhibitor ID-3 (ID3).	[62]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride decreases the expression of DNA-binding protein inhibitor ID-3 (ID3).	[63]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE decreases the expression of DNA-binding protein inhibitor ID-3 (ID3).	[25]
Resorcinol	DMM37C0	Investigative	Resorcinol decreases the expression of DNA-binding protein inhibitor ID-3 (ID3).	[64]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid increases the expression of DNA-binding protein inhibitor ID-3 (ID3).	[65]
Arachidonic acid	DMUOQZD	Investigative	Arachidonic acid decreases the expression of DNA-binding protein inhibitor ID-3 (ID3).	[66]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of DNA-binding protein inhibitor ID-3 (ID3).	[53]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of DNA-binding protein inhibitor ID-3 (ID3).	[56]

References

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