Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB97VIK)

• DOT Name: Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3)
• Synonyms: IGF2 mRNA-binding protein 3; IMP-3; IGF-II mRNA-binding protein 3; KH domain-containing protein overexpressed in cancer; hKOC; VICKZ family member 3
• Gene Name: IGF2BP3
• Related Disease:
  Epithelial ovarian cancer
  Ovarian cancer
  Ovarian neoplasm
  Acute lymphocytic leukaemia
  Advanced cancer
  Barrett esophagus
  Breast neoplasm
  Childhood acute lymphoblastic leukemia
  Cholangiocarcinoma
  Colorectal carcinoma
  Esophageal squamous cell carcinoma
  Ewing sarcoma
  Gastric neoplasm
  Glioma
  leukaemia
  Leukemia
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Malignant mesothelioma
  Metastatic malignant neoplasm
  Neoplasm
  Neuroendocrine cancer
  Non-small-cell lung cancer
  Osteosarcoma
  Peritoneal neoplasm
  Renal cell carcinoma
  Triple negative breast cancer
  Breast cancer
  Breast carcinoma
  Gastric cancer
  Glioblastoma multiforme
  Melanoma
  Squamous cell carcinoma
  Stomach cancer
  Adenocarcinoma
  Hepatocellular carcinoma
  Lymphoma
  Matthew-Wood syndrome
  Non-insulin dependent diabetes
  Pancreatic cancer
  Pancreatic ductal carcinoma
  Thyroid cancer
  Thyroid gland carcinoma
  Thyroid tumor
• UniProt ID: IF2B3_HUMAN
• PDB ID: 2E44; 6FQ1; 6FQR; 6GQE; 6GX6
• Pfam ID: PF00013 ; PF00076
• Sequence:
  MNKLYIGNLSENAAPSDLESIFKDAKIPVSGPFLVKTGYAFVDCPDESWALKAIEALSGK
  IELHGKPIEVEHSVPKRQRIRKLQIRNIPPHLQWEVLDSLLVQYGVVESCEQVNTDSETA
  VVNVTYSSKDQARQALDKLNGFQLENFTLKVAYIPDEMAAQQNPLQQPRGRRGLGQRGSS
  RQGSPGSVSKQKPCDLPLRLLVPTQFVGAIIGKEGATIRNITKQTQSKIDVHRKENAGAA
  EKSITILSTPEGTSAACKSILEIMHKEAQDIKFTEEIPLKILAHNNFVGRLIGKEGRNLK
  KIEQDTDTKITISPLQELTLYNPERTITVKGNVETCAKAEEEIMKKIRESYENDIASMNL
  QAHLIPGLNLNALGLFPPTSGMPPPTSGPPSAMTPPYPQFEQSETETVHLFIPALSVGAI
  IGKQGQHIKQLSRFAGASIKIAPAEAPDAKVRMVIITGPPEAQFKAQGRIYGKIKEENFV
  SPKEEVKLEAHIRVPSFAAGRVIGKGGKTVNELQNLSSAEVVVPRDQTPDENDQVVVKIT
  GHFYACQVAQRKIQEILTQVKQHQQQKALQSGPPQSRRK
• Function: RNA-binding factor that may recruit target transcripts to cytoplasmic protein-RNA complexes (mRNPs). This transcript 'caging' into mRNPs allows mRNA transport and transient storage. It also modulates the rate and location at which target transcripts encounter the translational apparatus and shields them from endonuclease attacks or microRNA-mediated degradation. Preferentially binds to N6-methyladenosine (m6A)-containing mRNAs and increases their stability. Binds to the 3'-UTR of CD44 mRNA and stabilizes it, hence promotes cell adhesion and invadopodia formation in cancer cells. Binds to beta-actin/ACTB and MYC transcripts. Increases MYC mRNA stability by binding to the coding region instability determinant (CRD) and binding is enhanced by m6A-modification of the CRD. Binds to the 5'-UTR of the insulin-like growth factor 2 (IGF2) mRNAs.
• Tissue Specificity: Expressed in fetal liver, fetal lung, fetal kidney, fetal thymus, fetal placenta, fetal follicles of ovary and gonocytes of testis, growing oocytes, spermatogonia and semen (at protein level). Expressed in cervix adenocarcinoma, in testicular, pancreatic and renal-cell carcinomas (at protein level). Expressed ubiquitously during fetal development at 8 and 14 weeks of gestation. Expressed in ovary, testis, brain, placenta, pancreatic cancer tissues and pancreatic cancer cell lines.
• Reactome Pathway: Insulin-like Growth Factor-2 mRNA Binding Proteins (IGF2BPs/IMPs/VICKZs) bind RNA (R-HSA-428359)

Molecular Interaction Atlas (MIA) of This DOT

45 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Epithelial ovarian cancer	DIS56MH2	Definitive	Biomarker	[1]
Ovarian cancer	DISZJHAP	Definitive	Biomarker	[1]
Ovarian neoplasm	DISEAFTY	Definitive	Biomarker	[1]
Acute lymphocytic leukaemia	DISPX75S	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Barrett esophagus	DIS416Y7	Strong	Biomarker	[4]
Breast neoplasm	DISNGJLM	Strong	Posttranslational Modification	[5]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Strong	Biomarker	[2]
Cholangiocarcinoma	DIS71F6X	Strong	Altered Expression	[6]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[7]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[8]
Ewing sarcoma	DISQYLV3	Strong	Biomarker	[9]
Gastric neoplasm	DISOKN4Y	Strong	Altered Expression	[10]
Glioma	DIS5RPEH	Strong	Biomarker	[11]
leukaemia	DISS7D1V	Strong	Biomarker	[2]
Leukemia	DISNAKFL	Strong	Biomarker	[2]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[12]
Lung cancer	DISCM4YA	Strong	Altered Expression	[12]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[12]
Malignant mesothelioma	DISTHJGH	Strong	Biomarker	[13]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[14]
Neoplasm	DISZKGEW	Strong	Altered Expression	[15]
Neuroendocrine cancer	DISVGJET	Strong	Altered Expression	[16]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[15]
Osteosarcoma	DISLQ7E2	Strong	Altered Expression	[17]
Peritoneal neoplasm	DIS2ZMIF	Strong	Biomarker	[13]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[18]
Triple negative breast cancer	DISAMG6N	Strong	Altered Expression	[19]
Breast cancer	DIS7DPX1	moderate	Biomarker	[20]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[20]
Gastric cancer	DISXGOUK	moderate	Altered Expression	[21]
Glioblastoma multiforme	DISK8246	moderate	Biomarker	[22]
Melanoma	DIS1RRCY	moderate	Altered Expression	[23]
Squamous cell carcinoma	DISQVIFL	moderate	Altered Expression	[24]
Stomach cancer	DISKIJSX	moderate	Altered Expression	[21]
Adenocarcinoma	DIS3IHTY	Limited	Biomarker	[25]
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[26]
Lymphoma	DISN6V4S	Limited	Altered Expression	[27]
Matthew-Wood syndrome	DISA7HR7	Limited	Biomarker	[28]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Genetic Variation	[29]
Pancreatic cancer	DISJC981	Limited	Altered Expression	[30]
Pancreatic ductal carcinoma	DIS26F9Q	Limited	Biomarker	[28]
Thyroid cancer	DIS3VLDH	Limited	Altered Expression	[31]
Thyroid gland carcinoma	DISMNGZ0	Limited	Altered Expression	[31]
Thyroid tumor	DISLVKMD	Limited	Biomarker	[31]

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Mitoxantrone	DMM39BF	Approved	Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) affects the response to substance of Mitoxantrone.	[51]
Cyclophosphamide	DM4O2Z7	Approved	Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) affects the response to substance of Cyclophosphamide.	[51]
Vinblastine	DM5TVS3	Approved	Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) affects the response to substance of Vinblastine.	[51]

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 Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3).	[32]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3).	[44]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3).	[50]

16 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 Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3).	[33]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3).	[34]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3).	[35]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3).	[36]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3).	[37]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3).	[38]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3).	[39]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3).	[40]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3).	[41]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3).	[42]
Berberine	DMC5Q8X	Phase 4	Berberine decreases the expression of Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3).	[43]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3).	[45]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3).	[46]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3).	[47]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3).	[48]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3).	[49]

References

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