Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTY4HVN8)

• DOT Name: Insulin-like growth factor-binding protein-like 1 (IGFBPL1)
• Synonyms: IGFBP-related protein 10; Insulin-like growth factor-binding-related protein 4; IGFBP-rP4
• Gene Name: IGFBPL1
• Related Disease:
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Carcinoma
  Depression
  Major depressive disorder
• UniProt ID: IBPL1_HUMAN
• PDB ID: 7MJ6; 7MJ7; 7MJ8; 7MJ9
• Pfam ID: PF07679 ; PF00219 ; PF07648
• Sequence:
  MPRLSLLLPLLLLLLLPLLPPLSPSLGIRDVGGRRPKCGPCRPEGCPAPAPCPAPGISAL
  DECGCCARCLGAEGASCGGRAGGRCGPGLVCASQAAGAAPEGTGLCVCAQRGTVCGSDGR
  SYPSVCALRLRARHTPRAHPGHLHKARDGPCEFAPVVVVPPRSVHNVTGAQVGLSCEVRA
  VPTPVITWRKVTKSPEGTQALEELPGDHVNIAVQVRGGPSDHEATAWILINPLRKEDEGV
  YQCHAANMVGEAESHSTVTVLDLSKYRSFHFPAPDDRM
• Function: IGF-binding proteins prolong the half-life of IGFs and have been shown to either inhibit or stimulate the growth promoting effects of the IGFs in cell culture. They alter the interaction of IGFs with their cell surface receptors. May be a putative tumor suppressor protein.
• Tissue Specificity: Expressed at the highest level in both brain and testis, with lower levels in the prostate, bladder and lung.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Posttranslational Modification	[1]
Breast cancer	DIS7DPX1	Strong	Posttranslational Modification	[1]
Breast carcinoma	DIS2UE88	Strong	Posttranslational Modification	[1]
Breast neoplasm	DISNGJLM	Strong	Posttranslational Modification	[1]
Carcinoma	DISH9F1N	Strong	Posttranslational Modification	[1]
Depression	DIS3XJ69	Strong	Genetic Variation	[2]
Major depressive disorder	DIS4CL3X	Strong	Biomarker	[2]

7 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 Insulin-like growth factor-binding protein-like 1 (IGFBPL1).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Insulin-like growth factor-binding protein-like 1 (IGFBPL1).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Insulin-like growth factor-binding protein-like 1 (IGFBPL1).	[5]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Insulin-like growth factor-binding protein-like 1 (IGFBPL1).	[6]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Insulin-like growth factor-binding protein-like 1 (IGFBPL1).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Insulin-like growth factor-binding protein-like 1 (IGFBPL1).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Insulin-like growth factor-binding protein-like 1 (IGFBPL1).	[10]

1 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 Insulin-like growth factor-binding protein-like 1 (IGFBPL1).	[8]

References

• [1] Epigenetic inactivation implies independent functions for insulin-like growth factor binding protein (IGFBP)-related protein 1 and the related IGFBPL1 in inhibiting breast cancer phenotypes.Clin Cancer Res. 2007 Jul 15;13(14):4061-8. doi: 10.1158/1078-0432.CCR-06-3052.
• [2] IGF-I in major depression and antidepressant treatment response.Eur Neuropsychopharmacol. 2015 Jun;25(6):864-72. doi: 10.1016/j.euroneuro.2014.12.013. Epub 2015 Jan 5.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [5] Editor's Highlight: Transcriptome Profiling Reveals Bisphenol A Alternatives Activate Estrogen Receptor Alpha in Human Breast Cancer Cells. Toxicol Sci. 2017 Aug 1;158(2):431-443. doi: 10.1093/toxsci/kfx101.
• [6] Gene expression signatures after ethanol exposure in differentiating embryoid bodies. Toxicol In Vitro. 2018 Feb;46:66-76.
• [7] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [8] 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.
• [9] 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.
• [10] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.