Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTT666SJ)

• DOT Name: Odontogenic ameloblast-associated protein (ODAM)
• Synonyms: Apin
• Gene Name: ODAM
• Related Disease:
  Amyloidosis
  Colorectal carcinoma
  Epithelial neoplasm
  Exanthem
  Gastric cancer
  Periodontitis
  Stomach cancer
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Melanoma
  Neoplasm
  Periodontal disease
  Tricho-dento-osseous syndrome
• UniProt ID: ODAM_HUMAN
• Pfam ID: PF15424
• Sequence:
  MKIIILLGFLGATLSAPLIPQRLMSASNSNELLLNLNNGQLLPLQLQGPLNSWIPPFSGI
  LQQQQQAQIPGLSQFSLSALDQFAGLLPNQIPLTGEASFAQGAQAGQVDPLQLQTPPQTQ
  PGPSHVMPYVFSFKMPQEQGQMFQYYPVYMVLPWEQPQQTVPRSPQQTRQQQYEEQIPFY
  AQFGYIPQLAEPAISGGQQQLAFDPQLGTAPEIAVMSTGEEIPYLQKEAINFRHDSAGVF
  MPSTSPKPSTTNVFTSAVDQTITPELPEEKDKTDSLREP
• Function: Tooth-associated epithelia protein that probably plays a role in odontogenesis, the complex process that results in the initiation and generation of the tooth. May be incorporated in the enamel matrix at the end of mineralization process. Involved in the induction of RHOA activity via interaction with ARHGEF and expression of downstream factors such as ROCK. Plays a role in attachment of the junctional epithelium to the tooth surface.
• Tissue Specificity: Expressed in the junctional epithelium of healthy teeth. In periodontitis, absent in the pocket epithelium of the diseased periodontium but is detected in the gingival crevicular fluid.
• Reactome Pathway: Amyloid fiber formation (R-HSA-977225)

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Amyloidosis	DISHTAI2	Strong	Biomarker	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[2]
Epithelial neoplasm	DIS0T594	Strong	Biomarker	[2]
Exanthem	DISAFOQN	Strong	Altered Expression	[3]
Gastric cancer	DISXGOUK	Strong	Biomarker	[4]
Periodontitis	DISI9JOI	Strong	Biomarker	[5]
Stomach cancer	DISKIJSX	Strong	Biomarker	[4]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[6]
Breast cancer	DIS7DPX1	moderate	Biomarker	[6]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[6]
Melanoma	DIS1RRCY	moderate	Biomarker	[7]
Neoplasm	DISZKGEW	moderate	Altered Expression	[7]
Periodontal disease	DISJQHVN	Limited	Biomarker	[5]
Tricho-dento-osseous syndrome	DISXZOGV	Limited	Genetic Variation	[8]

13 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 Odontogenic ameloblast-associated protein (ODAM).	[9]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Odontogenic ameloblast-associated protein (ODAM).	[10]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Odontogenic ameloblast-associated protein (ODAM).	[11]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Odontogenic ameloblast-associated protein (ODAM).	[12]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Odontogenic ameloblast-associated protein (ODAM).	[13]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Odontogenic ameloblast-associated protein (ODAM).	[14]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Odontogenic ameloblast-associated protein (ODAM).	[14]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Odontogenic ameloblast-associated protein (ODAM).	[15]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Odontogenic ameloblast-associated protein (ODAM).	[16]
Malathion	DMXZ84M	Approved	Malathion decreases the expression of Odontogenic ameloblast-associated protein (ODAM).	[17]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Odontogenic ameloblast-associated protein (ODAM).	[18]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Odontogenic ameloblast-associated protein (ODAM).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Odontogenic ameloblast-associated protein (ODAM).	[19]

References

• [1] Expression of odontogenic ameloblast-associated protein (ODAM) in dental and other epithelial neoplasms.Mol Med. 2008 May-Jun;14(5-6):318-26. doi: 10.2119/2008-00010.Kestler.
• [2] Odontogenic ameloblast-associated protein (ODAM) inhibits human colorectal cancer growth by promoting PTEN elevation and inactivating PI3K/AKT signaling.Biomed Pharmacother. 2016 Dec;84:601-607. doi: 10.1016/j.biopha.2016.09.076. Epub 2016 Sep 29.
• [3] Expression of odontogenic ameloblast-associated protein in the dental follicle and its role in osteogenic differentiation of dental follicle stem cells.Arch Oral Biol. 2017 Jun;78:6-12. doi: 10.1016/j.archoralbio.2017.02.001. Epub 2017 Feb 5.
• [4] Systematic search for gastric cancer-specific genes based on SAGE data: melanoma inhibitory activity and matrix metalloproteinase-10 are novel prognostic factors in patients with gastric cancer.Oncogene. 2006 Apr 20;25(17):2546-57. doi: 10.1038/sj.onc.1209279.
• [5] The sensitive detection of ODAM by using sandwich-type biosensors with a cognate pair of aptamers for the early diagnosis of periodontal disease.Biosens Bioelectron. 2019 Feb 1;126:122-128. doi: 10.1016/j.bios.2018.10.040. Epub 2018 Oct 23.
• [6] ODAM inhibits RhoA-dependent invasion in breast cancer.Cell Biochem Funct. 2015 Oct;33(7):451-61. doi: 10.1002/cbf.3132. Epub 2015 Sep 10.
• [7] Odontogenic ameloblast-associated protein (ODAM) inhibits growth and migration of human melanoma cells and elicits PTEN elevation and inactivation of PI3K/AKT signaling.BMC Cancer. 2013 May 7;13:227. doi: 10.1186/1471-2407-13-227.
• [8] Transcriptional factor DLX3 promotes the gene expression of enamel matrix proteins during amelogenesis.PLoS One. 2015 Mar 27;10(3):e0121288. doi: 10.1371/journal.pone.0121288. eCollection 2015.
• [9] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [10] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [11] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [12] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [13] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [14] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [15] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [16] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [17] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [18] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [19] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.