Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVWT6JZ)

• DOT Name: Disintegrin and metalloproteinase domain-containing protein 23 (ADAM23)
• Synonyms: ADAM 23; Metalloproteinase-like, disintegrin-like, and cysteine-rich protein 3; MDC-3
• Gene Name: ADAM23
• Related Disease:
  Breast neoplasm
  Epilepsy
  Adult glioblastoma
  Brain neoplasm
  Epithelial ovarian cancer
  Familial adenomatous polyposis
  Gastric cancer
  Gastric neoplasm
  Glioblastoma multiforme
  Glioma
  Head and neck cancer
  Head and neck carcinoma
  Immunodeficiency
  Laryngeal disorder
  Meningioma
  Metastatic malignant neoplasm
  Neoplasm
  Non-small-cell lung cancer
  Plasma cell myeloma
  Stomach cancer
  Neuroblastoma
  Acute myelogenous leukaemia
  Advanced cancer
  Brain cancer
  Breast cancer
  Breast carcinoma
  Colorectal carcinoma
  Colorectal neoplasm
• UniProt ID: ADA23_HUMAN
• Pfam ID: PF08516 ; PF00200 ; PF07974 ; PF01562 ; PF01421
• Sequence:
  MKPPGSSSRQPPLAGCSLAGASCGPQRGPAGSVPASAPARTPPCRLLLVLLLLPPLAASS
  RPRAWGAAAPSAPHWNETAEKNLGVLADEDNTLQQNSSSNISYSNAMQKEITLPSRLIYY
  INQDSESPYHVLDTKARHQQKHNKAVHLAQASFQIEAFGSKFILDLILNNGLLSSDYVEI
  HYENGKPQYSKGGEHCYYHGSIRGVKDSKVALSTCNGLHGMFEDDTFVYMIEPLELVHDE
  KSTGRPHIIQKTLAGQYSKQMKNLTMERGDQWPFLSELQWLKRRKRAVNPSRGIFEEMKY
  LELMIVNDHKTYKKHRSSHAHTNNFAKSVVNLVDSIYKEQLNTRVVLVAVETWTEKDQID
  ITTNPVQMLHEFSKYRQRIKQHADAVHLISRVTFHYKRSSLSYFGGVCSRTRGVGVNEYG
  LPMAVAQVLSQSLAQNLGIQWEPSSRKPKCDCTESWGGCIMEETGVSHSRKFSKCSILEY
  RDFLQRGGGACLFNRPTKLFEPTECGNGYVEAGEECDCGFHVECYGLCCKKCSLSNGAHC
  SDGPCCNNTSCLFQPRGYECRDAVNECDITEYCTGDSGQCPPNLHKQDGYACNQNQGRCY
  NGECKTRDNQCQYIWGTKAAGSDKFCYEKLNTEGTEKGNCGKDGDRWIQCSKHDVFCGFL
  LCTNLTRAPRIGQLQGEIIPTSFYHQGRVIDCSGAHVVLDDDTDVGYVEDGTPCGPSMMC
  LDRKCLQIQALNMSSCPLDSKGKVCSGHGVCSNEATCICDFTWAGTDCSIRDPVRNLHPP
  KDEGPKGPSATNLIIGSIAGAILVAAIVLGGTGWGFKNVKKRRFDPTQQGPI
• Function: May play a role in cell-cell and cell-matrix interactions. This is a non-catalytic metalloprotease-like protein.
• Tissue Specificity: Highly expressed in the brain and weakly expressed in the heart. In the brain, expressed prominently in the amygdala, caudate nucleus, hypothalamus, thalamus, cerebral cortex and occipital pole.
• Reactome Pathway: LGI-ADAM interactions (R-HSA-5682910)

Molecular Interaction Atlas (MIA) of This DOT

28 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast neoplasm	DISNGJLM	Definitive	Biomarker	[1]
Epilepsy	DISBB28L	Definitive	Biomarker	[2]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[3]
Brain neoplasm	DISY3EKS	Strong	Genetic Variation	[4]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[5]
Familial adenomatous polyposis	DISW53RE	Strong	Genetic Variation	[6]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[7]
Gastric neoplasm	DISOKN4Y	Strong	Posttranslational Modification	[7]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[3]
Glioma	DIS5RPEH	Strong	Altered Expression	[8]
Head and neck cancer	DISBPSQZ	Strong	Biomarker	[9]
Head and neck carcinoma	DISOU1DS	Strong	Biomarker	[9]
Immunodeficiency	DIS093I0	Strong	Altered Expression	[10]
Laryngeal disorder	DISDKUQO	Strong	Biomarker	[9]
Meningioma	DISPT4TG	Strong	Biomarker	[3]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[3]
Neoplasm	DISZKGEW	Strong	Posttranslational Modification	[11]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[12]
Plasma cell myeloma	DIS0DFZ0	Strong	Altered Expression	[13]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[7]
Neuroblastoma	DISVZBI4	moderate	Altered Expression	[14]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[15]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[11]
Brain cancer	DISBKFB7	Limited	Genetic Variation	[4]
Breast cancer	DIS7DPX1	Limited	Biomarker	[11]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[11]
Colorectal carcinoma	DIS5PYL0	Limited	Posttranslational Modification	[4]
Colorectal neoplasm	DISR1UCN	Limited	Posttranslational Modification	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Disintegrin and metalloproteinase domain-containing protein 23 (ADAM23).	[16]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Disintegrin and metalloproteinase domain-containing protein 23 (ADAM23).	[17]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Disintegrin and metalloproteinase domain-containing protein 23 (ADAM23).	[18]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Disintegrin and metalloproteinase domain-containing protein 23 (ADAM23).	[19]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Disintegrin and metalloproteinase domain-containing protein 23 (ADAM23).	[20]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Disintegrin and metalloproteinase domain-containing protein 23 (ADAM23).	[21]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Disintegrin and metalloproteinase domain-containing protein 23 (ADAM23).	[22]
cinnamaldehyde	DMZDUXG	Investigative	cinnamaldehyde increases the expression of Disintegrin and metalloproteinase domain-containing protein 23 (ADAM23).	[24]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Disintegrin and metalloproteinase domain-containing protein 23 (ADAM23).	[23]

References

• [1] Intratumoral heterogeneity of ADAM23 promotes tumor growth and metastasis through LGI4 and nitric oxide signals.Oncogene. 2015 Mar 5;34(10):1270-9. doi: 10.1038/onc.2014.70. Epub 2014 Mar 24.
• [2] ADAM23 is a common risk gene for canine idiopathic epilepsy.BMC Genet. 2017 Jan 31;18(1):8. doi: 10.1186/s12863-017-0478-6.
• [3] ADAM23 methylation and expression analysis in brain tumors.Neurosci Lett. 2005 Jun 3;380(3):260-4. doi: 10.1016/j.neulet.2005.01.050. Epub 2005 Feb 8.
• [4] Promoter hypermethylation of the ADAM23 gene in colorectal cancer cell lines and cancer tissues.Int J Cancer. 2009 Mar 15;124(6):1258-62. doi: 10.1002/ijc.24023.
• [5] Low levels of ADAM23 expression in epithelial ovarian cancer are associated with poor survival.Pathol Res Pract. 2018 Aug;214(8):1115-1122. doi: 10.1016/j.prp.2018.06.007. Epub 2018 Jun 12.
• [6] CXCL12 and ADAM23 hypermethylation are associated with advanced breast cancers.Transl Res. 2015 Jun;165(6):717-30. doi: 10.1016/j.trsl.2014.12.006. Epub 2015 Jan 9.
• [7] ADAM23, a possible tumor suppressor gene, is frequently silenced in gastric cancers by homozygous deletion or aberrant promoter hypermethylation.Oncogene. 2005 Dec 1;24(54):8051-60. doi: 10.1038/sj.onc.1208952.
• [8] Leucine-rich glioma inactivated 3: integrative analyses support its prognostic role in glioma.Onco Targets Ther. 2017 May 24;10:2721-2728. doi: 10.2147/OTT.S138912. eCollection 2017.
• [9] Methylation profile of genes CDKN2A (p14 and p16), DAPK1, CDH1, and ADAM23 in head and neck cancer.Cancer Genet Cytogenet. 2007 Feb;173(1):31-7. doi: 10.1016/j.cancergencyto.2006.09.008.
• [10] ADAM23 negatively modulates alpha(v)beta(3) integrin activation during metastasis.Cancer Res. 2009 Jul 1;69(13):5546-52. doi: 10.1158/0008-5472.CAN-08-2976. Epub 2009 Jun 23.
• [11] A disintegrin and metalloprotease 23 hypermethylation predicts decreased disease-free survival in low-risk breast cancer patients.Cancer Sci. 2019 May;110(5):1695-1704. doi: 10.1111/cas.13985. Epub 2019 Mar 18.
• [12] The expression of ADAM23 and its correlation with promoter methylation in non-small-cell lung carcinoma.Int J Exp Pathol. 2011 Oct;92(5):333-9. doi: 10.1111/j.1365-2613.2011.00766.x. Epub 2011 Mar 23.
• [13] Gene expression profile of ADAMs and ADAMTSs metalloproteinases in normal and malignant plasma cells and in the bone marrow environment.Exp Hematol. 2011 May;39(5):546-557.e8. doi: 10.1016/j.exphem.2011.02.002. Epub 2011 Mar 3.
• [14] Characterization of a specific interaction between ADAM23 and cellular prion protein.Neurosci Lett. 2009 Sep 11;461(1):16-20. doi: 10.1016/j.neulet.2009.05.049. Epub 2009 May 27.
• [15] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [16] Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
• [17] 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.
• [18] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [19] 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.
• [20] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [21] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [22] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [23] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [24] Comparative DNA microarray analysis of human monocyte derived dendritic cells and MUTZ-3 cells exposed to the moderate skin sensitizer cinnamaldehyde. Toxicol Appl Pharmacol. 2009 Sep 15;239(3):273-83.