Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPTVW5W)

• DOT Name: Disintegrin and metalloproteinase domain-containing protein 11 (ADAM11)
• Synonyms: ADAM 11; Metalloproteinase-like, disintegrin-like, and cysteine-rich protein; MDC
• Gene Name: ADAM11
• Related Disease:
  Neoplasm
  Adult T-cell leukemia/lymphoma
  Cardiovascular disease
  Classic Hodgkin lymphoma
  Exanthem
  HIV infectious disease
  Non-insulin dependent diabetes
  Obesity
  Psoriatic arthritis
  Rheumatoid arthritis
  Schizophrenia
  T-cell leukaemia
  Tuberculosis
  Advanced cancer
  Breast cancer
  Breast carcinoma
  High blood pressure
  Lung cancer
  Lung carcinoma
  Atopic dermatitis
  Rectal carcinoma
  Type-1/2 diabetes
• UniProt ID: ADA11_HUMAN
• Pfam ID: PF08516 ; PF00200 ; PF07974 ; PF01562 ; PF01421
• Sequence:
  MRLLRRWAFAALLLSLLPTPGLGTQGPAGALRWGGLPQLGGPGAPEVTEPSRLVRESSGG
  EVRKQQLDTRVRQEPPGGPPVHLAQVSFVIPAFNSNFTLDLELNHHLLSSQYVERHFSRE
  GTTQHSTGAGDHCYYQGKLRGNPHSFAALSTCQGLHGVFSDGNLTYIVEPQEVAGPWGAP
  QGPLPHLIYRTPLLPDPLGCREPGCLFAVPAQSAPPNRPRLRRKRQVRRGHPTVHSETKY
  VELIVINDHQLFEQMRQSVVLTSNFAKSVVNLADVIYKEQLNTRIVLVAMETWADGDKIQ
  VQDDLLETLARLMVYRREGLPEPSDATHLFSGRTFQSTSSGAAYVGGICSLSHGGGVNEY
  GNMGAMAVTLAQTLGQNLGMMWNKHRSSAGDCKCPDIWLGCIMEDTGFYLPRKFSRCSID
  EYNQFLQEGGGSCLFNKPLKLLDPPECGNGFVEAGEECDCGSVQECSRAGGNCCKKCTLT
  HDAMCSDGLCCRRCKYEPRGVSCREAVNECDIAETCTGDSSQCPPNLHKLDGYYCDHEQG
  RCYGGRCKTRDRQCQVLWGHAAADRFCYEKLNVEGTERGSCGRKGSGWVQCSKQDVLCGF
  LLCVNISGAPRLGDLVGDISSVTFYHQGKELDCRGGHVQLADGSDLSYVEDGTACGPNML
  CLDHRCLPASAFNFSTCPGSGERRICSHHGVCSNEGKCICQPDWTGKDCSIHNPLPTSPP
  TGETERYKGPSGTNIIIGSIAGAVLVAAIVLGGTGWGFKNIRRGRSGGA
• Function: Probable ligand for integrin in the brain. This is a non catalytic metalloprotease-like protein. Required for localization of the potassium channel subunit proteins KCNA1/KV1.1 and KCNA2/KV1.2 at cerebellar cortex basket cell distal terminals, is thereby involved in ephaptic inhibitory synchronization of Purkinje cell firing and response to stress. Plays a role in spatial learning and motor coordination. Involved in the nociceptive pain response to chemical-derived stimulation.
• Tissue Specificity: Expressed predominantly in brain. Slightly detected or not at all in other tissues.
• Reactome Pathway: LGI-ADAM interactions (R-HSA-5682910)

Molecular Interaction Atlas (MIA) of This DOT

22 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Genetic Variation	[1]
Adult T-cell leukemia/lymphoma	DIS882XU	Strong	Biomarker	[2]
Cardiovascular disease	DIS2IQDX	Strong	Biomarker	[3]
Classic Hodgkin lymphoma	DISV1LU6	Strong	Altered Expression	[4]
Exanthem	DISAFOQN	Strong	Biomarker	[5]
HIV infectious disease	DISO97HC	Strong	Altered Expression	[6]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[7]
Obesity	DIS47Y1K	Strong	Genetic Variation	[8]
Psoriatic arthritis	DISLWTG2	Strong	Biomarker	[9]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[9]
Schizophrenia	DISSRV2N	Strong	Altered Expression	[10]
T-cell leukaemia	DISJ6YIF	Strong	Biomarker	[2]
Tuberculosis	DIS2YIMD	Strong	Altered Expression	[11]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[12]
Breast cancer	DIS7DPX1	moderate	Biomarker	[13]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[13]
High blood pressure	DISY2OHH	moderate	Genetic Variation	[14]
Lung cancer	DISCM4YA	moderate	Biomarker	[15]
Lung carcinoma	DISTR26C	moderate	Biomarker	[15]
Atopic dermatitis	DISTCP41	Limited	Biomarker	[16]
Rectal carcinoma	DIS8FRR7	Limited	Biomarker	[17]
Type-1/2 diabetes	DISIUHAP	Limited	Genetic Variation	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Disintegrin and metalloproteinase domain-containing protein 11 (ADAM11).	[18]
Malathion	DMXZ84M	Approved	Malathion increases the methylation of Disintegrin and metalloproteinase domain-containing protein 11 (ADAM11).	[20]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Disintegrin and metalloproteinase domain-containing protein 11 (ADAM11).	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Disintegrin and metalloproteinase domain-containing protein 11 (ADAM11).	[19]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Disintegrin and metalloproteinase domain-containing protein 11 (ADAM11).	[22]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Disintegrin and metalloproteinase domain-containing protein 11 (ADAM11).	[23]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Disintegrin and metalloproteinase domain-containing protein 11 (ADAM11).	[24]

References

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• [2] Frequent expression of CCR4 in adult T-cell leukemia and human T-cell leukemia virus type 1-transformed T cells.Blood. 2002 Mar 1;99(5):1505-11. doi: 10.1182/blood.v99.5.1505.
• [3] Plasma lipid composition and risk of developing cardiovascular disease.PLoS One. 2013 Aug 15;8(8):e71846. doi: 10.1371/journal.pone.0071846. eCollection 2013.
• [4] Serum chemokine levels in Hodgkin lymphoma patients: highly increased levels of CCL17 and CCL22.Br J Haematol. 2008 Mar;140(5):527-36. doi: 10.1111/j.1365-2141.2007.06964.x.
• [5] Up-regulation of CCL17, CCL22 and CCR4 in drug-induced maculopapular exanthema.Clin Exp Allergy. 2007 May;37(5):704-13. doi: 10.1111/j.1365-2222.2007.02699.x.
• [6] Cocaine modulates dendritic cell-specific C type intercellular adhesion molecule-3-grabbing nonintegrin expression by dendritic cells in HIV-1 patients.J Immunol. 2005 Jun 1;174(11):6617-26. doi: 10.4049/jimmunol.174.11.6617.
• [7] Dimethylguanidino Valerate: A Lifestyle-Related Metabolite Associated With Future Coronary Artery Disease and Cardiovascular Mortality.J Am Heart Assoc. 2019 Oct;8(19):e012846. doi: 10.1161/JAHA.119.012846. Epub 2019 Sep 19.
• [8] Do Genetic Factors Modify the Relationship Between Obesity and Hypertriglyceridemia? Findings From the GLACIER and the MDC Studies.Circ Cardiovasc Genet. 2016 Apr;9(2):162-71. doi: 10.1161/CIRCGENETICS.115.001218. Epub 2016 Feb 10.
• [9] Expression of MDC/CCL22 and its receptor CCR4 in rheumatoid arthritis, psoriatic arthritis and osteoarthritis.Cytokine. 2010 Jan;49(1):24-9. doi: 10.1016/j.cyto.2009.10.005. Epub 2009 Nov 25.
• [10] Abnormalities in chemokine levels in schizophrenia and their clinical correlates.Schizophr Res. 2017 Mar;181:63-69. doi: 10.1016/j.schres.2016.09.019. Epub 2016 Sep 17.
• [11] Diagnostic performance of plasma cytokine biosignature combination and MCP-1 as individual biomarkers for differentiating stages Mycobacterium tuberculosis infection.J Infect. 2019 Apr;78(4):281-291. doi: 10.1016/j.jinf.2018.10.017. Epub 2018 Dec 5.
• [12] Cystatin C and Risk of Diabetes and the Metabolic Syndrome - Biomarker and Genotype Association Analyses.PLoS One. 2016 May 24;11(5):e0155735. doi: 10.1371/journal.pone.0155735. eCollection 2016.
• [13] Phospho-ibuprofen (MDC-917) suppresses breast cancer growth: an effect controlled by the thioredoxin system.Breast Cancer Res. 2012 Jan 31;14(1):R20. doi: 10.1186/bcr3105.
• [14] Vanin-1 T26I polymorphism, hypertension and cardiovascular events in two large urban-based prospective studies in Swedes.Nutr Metab Cardiovasc Dis. 2013 Jan;23(1):53-60. doi: 10.1016/j.numecd.2011.01.012. Epub 2011 May 6.
• [15] MiR-144 inhibits proliferation and induces apoptosis and autophagy in lung cancer cells by targeting TIGAR.Cell Physiol Biochem. 2015;35(3):997-1007. doi: 10.1159/000369755. Epub 2015 Feb 2.
• [16] Apamin inhibits TNF-- and IFN--induced inflammatory cytokines and chemokines via suppressions of NF-B signaling pathway and STAT in human keratinocytes.Pharmacol Rep. 2017 Oct;69(5):1030-1035. doi: 10.1016/j.pharep.2017.04.006. Epub 2017 Apr 18.
• [17] Multidisciplinary Conference and Clinical Management of Rectal Cancer.J Am Coll Surg. 2018 May;226(5):874-880. doi: 10.1016/j.jamcollsurg.2018.01.056. Epub 2018 Mar 23.
• [18] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [19] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [20] 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.
• [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] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [23] 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.
• [24] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.