Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTW878VI)

• DOT Name: Insulin-like growth factor-binding protein 6 (IGFBP6)
• Synonyms: IBP-6; IGF-binding protein 6; IGFBP-6
• Gene Name: IGFBP6
• UniProt ID: IBP6_HUMAN
• PDB ID: 1RMJ; 2JM2
• Pfam ID: PF00086
• Sequence:
  MTPHRLLPPLLLLLALLLAASPGGALARCPGCGQGVQAGCPGGCVEEEDGGSPAEGCAEA
  EGCLRREGQECGVYTPNCAPGLQCHPPKDDEAPLRALLLGRGRCLPARAPAVAEENPKES
  KPQAGTARPQDVNRRDQQRNPGTSTTPSQPNSAGVQDTEMGPCRRHLDSVLQQLQTEVYR
  GAQTLYVPNCDHRGFYRKRQCRSSQGQRRGPCWCVDRMGKSLPGSPDGNGSSSCPTGSSG
• Function: IGF-binding proteins prolong the half-life of the IGFs and have been shown to either inhibit or stimulate the growth promoting effects of the IGFs on cell culture. They alter the interaction of IGFs with their cell surface receptors. Activates the MAPK signaling pathway and induces cell migration.
• Reactome Pathway: Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) (R-HSA-381426)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
CYCLOPAMINE	DMEM2SW	Investigative	Insulin-like growth factor-binding protein 6 (IGFBP6) increases the response to substance of CYCLOPAMINE.	[28]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Insulin-like growth factor-binding protein 6 (IGFBP6).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Insulin-like growth factor-binding protein 6 (IGFBP6).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Insulin-like growth factor-binding protein 6 (IGFBP6).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Insulin-like growth factor-binding protein 6 (IGFBP6).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Insulin-like growth factor-binding protein 6 (IGFBP6).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Insulin-like growth factor-binding protein 6 (IGFBP6).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Insulin-like growth factor-binding protein 6 (IGFBP6).	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Insulin-like growth factor-binding protein 6 (IGFBP6).	[8]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Insulin-like growth factor-binding protein 6 (IGFBP6).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Insulin-like growth factor-binding protein 6 (IGFBP6).	[10]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Insulin-like growth factor-binding protein 6 (IGFBP6).	[11]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Insulin-like growth factor-binding protein 6 (IGFBP6).	[1]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Insulin-like growth factor-binding protein 6 (IGFBP6).	[12]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Insulin-like growth factor-binding protein 6 (IGFBP6).	[13]
Selenium	DM25CGV	Approved	Selenium increases the expression of Insulin-like growth factor-binding protein 6 (IGFBP6).	[14]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Insulin-like growth factor-binding protein 6 (IGFBP6).	[15]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Insulin-like growth factor-binding protein 6 (IGFBP6).	[16]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Insulin-like growth factor-binding protein 6 (IGFBP6).	[17]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Insulin-like growth factor-binding protein 6 (IGFBP6).	[18]
Menthol	DMG2KW7	Approved	Menthol increases the expression of Insulin-like growth factor-binding protein 6 (IGFBP6).	[19]
Simvastatin	DM30SGU	Approved	Simvastatin increases the expression of Insulin-like growth factor-binding protein 6 (IGFBP6).	[20]
Bexarotene	DMOBIKY	Approved	Bexarotene increases the expression of Insulin-like growth factor-binding protein 6 (IGFBP6).	[21]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Insulin-like growth factor-binding protein 6 (IGFBP6).	[14]
DNCB	DMDTVYC	Phase 2	DNCB increases the expression of Insulin-like growth factor-binding protein 6 (IGFBP6).	[22]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Insulin-like growth factor-binding protein 6 (IGFBP6).	[23]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Insulin-like growth factor-binding protein 6 (IGFBP6).	[24]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Insulin-like growth factor-binding protein 6 (IGFBP6).	[25]
LG100268	DM41RK2	Discontinued in Phase 1	LG100268 increases the expression of Insulin-like growth factor-binding protein 6 (IGFBP6).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Insulin-like growth factor-binding protein 6 (IGFBP6).	[26]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Insulin-like growth factor-binding protein 6 (IGFBP6).	[27]

References

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• [4] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
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• [7] Apoptosis-related mRNA expression profiles of ovarian cancer cell lines following cisplatin treatment. J Gynecol Oncol. 2010 Dec 30;21(4):255-61. doi: 10.3802/jgo.2010.21.4.255. Epub 2010 Dec 31.
• [8] Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells. Toxicol Appl Pharmacol. 2009 Nov 1;240(3):355-66.
• [9] The aquaglyceroporin AQP9 contributes to the sex-specific effects of in utero arsenic exposure on placental gene expression. Environ Health. 2017 Jun 14;16(1):59. doi: 10.1186/s12940-017-0267-8.
• [10] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [11] Ethinylestradiol and testosterone have divergent effects on circulating IGF system components in adolescents with constitutional tall stature. Eur J Endocrinol. 2005 Apr;152(4):597-604. doi: 10.1530/eje.1.01880.
• [12] Functional gene expression profile underlying methotrexate-induced senescence in human colon cancer cells. Tumour Biol. 2011 Oct;32(5):965-76.
• [13] Gene induction and apoptosis in human hepatocellular carci-noma cells SMMC-7721 exposed to 5-aza-2'-deoxycytidine. Chin Med J (Engl). 2007 Sep 20;120(18):1626-31.
• [14] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [15] Unique transcriptome, pathways, and networks in the human endometrial fibroblast response to progesterone in endometriosis. Biol Reprod. 2011 Apr;84(4):801-15.
• [16] Dissecting progressive stages of 5-fluorouracil resistance in vitro using RNA expression profiling. Int J Cancer. 2004 Nov 1;112(2):200-12. doi: 10.1002/ijc.20401.
• [17] Increased sensitivity for troglitazone-induced cytotoxicity using a human in vitro co-culture model. Toxicol In Vitro. 2009 Oct;23(7):1387-95.
• [18] Insulin-like growth factor binding protein-6 inhibits prostate cancer cell proliferation: implication for anticancer effect of diethylstilbestrol in hormone refractory prostate cancer. Br J Cancer. 2005 Apr 25;92(8):1538-44. doi: 10.1038/sj.bjc.6602520.
• [19] Repurposing L-menthol for systems medicine and cancer therapeutics? L-menthol induces apoptosis through caspase 10 and by suppressing HSP90. OMICS. 2016 Jan;20(1):53-64.
• [20] Simvastatin inactivates beta1-integrin and extracellular signal-related kinase signaling and inhibits cell proliferation in head and neck squamous cell carcinoma cells. Cancer Sci. 2007 Jun;98(6):890-9.
• [21] Identification of biomarkers modulated by the rexinoid LGD1069 (bexarotene) in human breast cells using oligonucleotide arrays. Cancer Res. 2006 Dec 15;66(24):12009-18.
• [22] Microarray analyses in dendritic cells reveal potential biomarkers for chemical-induced skin sensitization. Mol Immunol. 2007 May;44(12):3222-33.
• [23] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [24] The BET bromodomain inhibitor JQ1 suppresses growth of pancreatic ductal adenocarcinoma in patient-derived xenograft models. Oncogene. 2016 Feb 18;35(7):833-45.
• [25] 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.
• [26] The genomic response of Ishikawa cells to bisphenol A exposure is dose- and time-dependent. Toxicology. 2010 Apr 11;270(2-3):137-49. doi: 10.1016/j.tox.2010.02.008. Epub 2010 Feb 17.
• [27] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [28] Response to inhibition of smoothened in diverse epithelial cancer cells that lack smoothened or patched 1 mutations. Int J Oncol. 2012 Nov;41(5):1751-61. doi: 10.3892/ijo.2012.1599. Epub 2012 Aug 22.