Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJDHE17)

• DOT Name: Integrin beta-like protein 1 (ITGBL1)
• Synonyms: Osteoblast-specific cysteine-rich protein; Ten integrin EGF-like repeat domain-containing protein
• Gene Name: ITGBL1
• Related Disease:
  Arthritis
  Breast cancer
  Breast carcinoma
  Acute myelogenous leukaemia
  Advanced cancer
  Alzheimer disease
  Benign prostatic hyperplasia
  Epithelial ovarian cancer
  Neoplasm
  Non-small-cell lung cancer
  Ovarian cancer
  Ovarian neoplasm
  Prostate cancer
  Prostate carcinoma
  Prostate neoplasm
  Gastric cancer
  Stomach cancer
  Colorectal carcinoma
• UniProt ID: ITGBL_HUMAN
• Pfam ID: PF07974
• Sequence:
  MRPPGFRNFLLLASSLLFAGLSAVPQSFSPSLRSWPGAACRLSRAESERRCRAPGQPPGA
  ALCHGRGRCDCGVCICHVTEPGMFFGPLCECHEWVCETYDGSTCAGHGKCDCGKCKCDQG
  WYGDACQYPTNCDLTKKKSNQMCKNSQDIICSNAGTCHCGRCKCDNSDGSGLVYGKFCEC
  DDRECIDDETEEICGGHGKCYCGNCYCKAGWHGDKCEFQCDITPWESKRRCTSPDGKICS
  NRGTCVCGECTCHDVDPTGDWGDIHGDTCECDERDCRAVYDRYSDDFCSGHGQCNCGRCD
  CKAGWYGKKCEHPQSCTLSAEESIRKCQGSSDLPCSGRGKCECGKCTCYPPGDRRVYGKT
  CECDDRRCEDLDGVVCGGHGTCSCGRCVCERGWFGKLCQHPRKCNMTEEQSKNLCESADG
  ILCSGKGSCHCGKCICSAEEWYISGEFCDCDDRDCDKHDGLICTGNGICSCGNCECWDGW
  NGNACEIWLGSEYP
• Tissue Specificity: Widely expressed in many tissues, but readily detectable only in aorta.
• Reactome Pathway: RUNX2 regulates genes involved in cell migration (R-HSA-8941332)

Molecular Interaction Atlas (MIA) of This DOT

18 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Arthritis	DIST1YEL	Definitive	Altered Expression	[1]
Breast cancer	DIS7DPX1	Definitive	Altered Expression	[2]
Breast carcinoma	DIS2UE88	Definitive	Biomarker	[2]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[3]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[4]
Alzheimer disease	DISF8S70	Strong	Biomarker	[5]
Benign prostatic hyperplasia	DISI3CW2	Strong	Altered Expression	[6]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[4]
Neoplasm	DISZKGEW	Strong	Biomarker	[7]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[7]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[4]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[4]
Prostate cancer	DISF190Y	Strong	Biomarker	[8]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[8]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[6]
Gastric cancer	DISXGOUK	moderate	Biomarker	[9]
Stomach cancer	DISKIJSX	moderate	Biomarker	[9]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Integrin beta-like protein 1 (ITGBL1).	[11]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Integrin beta-like protein 1 (ITGBL1).	[12]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Integrin beta-like protein 1 (ITGBL1).	[13]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Integrin beta-like protein 1 (ITGBL1).	[14]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Integrin beta-like protein 1 (ITGBL1).	[15]
Folic acid	DMEMBJC	Approved	Folic acid increases the expression of Integrin beta-like protein 1 (ITGBL1).	[16]
Simvastatin	DM30SGU	Approved	Simvastatin decreases the expression of Integrin beta-like protein 1 (ITGBL1).	[17]
Rifampicin	DM5DSFZ	Approved	Rifampicin decreases the expression of Integrin beta-like protein 1 (ITGBL1).	[18]
Ibuprofen	DM8VCBE	Approved	Ibuprofen affects the expression of Integrin beta-like protein 1 (ITGBL1).	[19]
Rofecoxib	DM3P5DA	Approved	Rofecoxib affects the expression of Integrin beta-like protein 1 (ITGBL1).	[19]
PD-0325901	DM27D4J	Phase 2	PD-0325901 decreases the expression of Integrin beta-like protein 1 (ITGBL1).	[20]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Integrin beta-like protein 1 (ITGBL1).	[20]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Integrin beta-like protein 1 (ITGBL1).	[22]

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 Integrin beta-like protein 1 (ITGBL1).	[21]

References

• [1] ITGBL1 modulates integrin activity to promote cartilage formation and protect against arthritis.Sci Transl Med. 2018 Oct 10;10(462):eaam7486. doi: 10.1126/scitranslmed.aam7486.
• [2] ITGBL1 Is a Runx2 Transcriptional Target and Promotes Breast Cancer Bone Metastasis by Activating the TGF Signaling Pathway.Cancer Res. 2015 Aug 15;75(16):3302-13. doi: 10.1158/0008-5472.CAN-15-0240. Epub 2015 Jun 9.
• [3] Hypermethylation of ITGBL1 is associated with poor prognosis in acute myeloid leukemia.J Cell Physiol. 2019 Jun;234(6):9438-9446. doi: 10.1002/jcp.27629. Epub 2018 Oct 14.
• [4] Upregulation of ITGBL1 predicts poor prognosis and promotes chemoresistance in ovarian cancer.Cancer Biomark. 2020;27(1):51-61. doi: 10.3233/CBM-190460.
• [5] Cyclophilin D deficiency attenuates mitochondrial F1Fo ATP synthase dysfunction via OSCP in Alzheimer's disease.Neurobiol Dis. 2019 Jan;121:138-147. doi: 10.1016/j.nbd.2018.09.020. Epub 2018 Sep 26.
• [6] Molecular analyses of prostate tumors for diagnosis of malignancy on fine-needle aspiration biopsies.Oncotarget. 2017 Nov 6;8(62):104761-104771. doi: 10.18632/oncotarget.22289. eCollection 2017 Dec 1.
• [7] Epigenetic downregulated ITGBL1 promotes non-small cell lung cancer cell invasion through Wnt/PCP signaling.Tumour Biol. 2016 Feb;37(2):1663-9. doi: 10.1007/s13277-015-3919-8. Epub 2015 Aug 26.
• [8] ITGBL1 promotes EMT, invasion and migration by activating NF-B signaling pathway in prostate cancer.Onco Targets Ther. 2019 May 16;12:3753-3763. doi: 10.2147/OTT.S200082. eCollection 2019.
• [9] ITGBL1 Predicts a Poor Prognosis and Correlates EMT Phenotype in Gastric Cancer.J Cancer. 2017 Oct 17;8(18):3764-3773. doi: 10.7150/jca.20900. eCollection 2017.
• [10] Transcriptomic expression profiling identifies ITGBL1, an epithelial to mesenchymal transition (EMT)-associated gene, isa promising recurrence prediction biomarker in colorectal cancer.Mol Cancer. 2019 Feb 4;18(1):19. doi: 10.1186/s12943-019-0945-y.
• [11] Effects of progesterone treatment on expression of genes involved in uterine quiescence. Reprod Sci. 2011 Aug;18(8):781-97.
• [12] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [13] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [14] Methotrexate modulates folate phenotype and inflammatory profile in EA.hy 926 cells. Eur J Pharmacol. 2014 Jun 5;732:60-7.
• [15] Progesterone regulation of implantation-related genes: new insights into the role of oestrogen. Cell Mol Life Sci. 2007 Apr;64(7-8):1009-32.
• [16] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [17] 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.
• [18] Integrated analysis of rifampicin-induced microRNA and gene expression changes in human hepatocytes. Drug Metab Pharmacokinet. 2014;29(4):333-40.
• [19] Rofecoxib modulates multiple gene expression pathways in a clinical model of acute inflammatory pain. Pain. 2007 Mar;128(1-2):136-47.
• [20] PRC2 loss amplifies Ras-driven transcription and confers sensitivity to BRD4-based therapies. Nature. 2014 Oct 9;514(7521):247-51.
• [21] 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.
• [22] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.