Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT24S8YN)

• DOT Name: Disintegrin and metalloproteinase domain-containing protein 8 (ADAM8)
• Synonyms: ADAM 8; EC 3.4.24.-; Cell surface antigen MS2; CD antigen CD156a
• Gene Name: ADAM8
• UniProt ID: ADAM8_HUMAN
• PDB ID: 4DD8
• EC Number: 3.4.24.-
• Pfam ID: PF08516 ; PF00200 ; PF01562 ; PF01421
• Sequence:
  MRGLGLWLLGAMMLPAIAPSRPWALMEQYEVVLPWRLPGPRVRRALPSHLGLHPERVSYV
  LGATGHNFTLHLRKNRDLLGSGYTETYTAANGSEVTEQPRGQDHCFYQGHVEGYPDSAAS
  LSTCAGLRGFFQVGSDLHLIEPLDEGGEGGRHAVYQAEHLLQTAGTCGVSDDSLGSLLGP
  RTAAVFRPRPGDSLPSRETRYVELYVVVDNAEFQMLGSEAAVRHRVLEVVNHVDKLYQKL
  NFRVVLVGLEIWNSQDRFHVSPDPSVTLENLLTWQARQRTRRHLHDNVQLITGVDFTGTT
  VGFARVSAMCSHSSGAVNQDHSKNPVGVACTMAHEMGHNLGMDHDENVQGCRCQERFEAG
  RCIMAGSIGSSFPRMFSDCSQAYLESFLERPQSVCLANAPDLSHLVGGPVCGNLFVERGE
  QCDCGPPEDCRNRCCNSTTCQLAEGAQCAHGTCCQECKVKPAGELCRPKKDMCDLEEFCD
  GRHPECPEDAFQENGTPCSGGYCYNGACPTLAQQCQAFWGPGGQAAEESCFSYDILPGCK
  ASRYRADMCGVLQCKGGQQPLGRAICIVDVCHALTTEDGTAYEPVPEGTRCGPEKVCWKG
  RCQDLHVYRSSNCSAQCHNHGVCNHKQECHCHAGWAPPHCAKLLTEVHAASGSLPVFVVV
  VLVLLAVVLVTLAGIIVYRKARSRILSRNVAPKTTMGRSNPLFHQAASRVPAKGGAPAPS
  RGPQELVPTTHPGQPARHPASSVALKRPPPAPPVTVSSPPFPVPVYTRQAPKQVIKPTFA
  PPVPPVKPGAGAANPGPAEGAVGPKVALKPPIQRKQGAGAPTAP
• Function: Possible involvement in extravasation of leukocytes.
• Tissue Specificity: Expressed on neutrophils and monocytes.
• Reactome Pathway:
  Neutrophil degranulation (R-HSA-6798695)
  Degradation of the extracellular matrix (R-HSA-1474228)

Molecular Interaction Atlas (MIA) of This DOT

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 8 (ADAM8).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Disintegrin and metalloproteinase domain-containing protein 8 (ADAM8).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Disintegrin and metalloproteinase domain-containing protein 8 (ADAM8).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Disintegrin and metalloproteinase domain-containing protein 8 (ADAM8).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Disintegrin and metalloproteinase domain-containing protein 8 (ADAM8).	[3]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Disintegrin and metalloproteinase domain-containing protein 8 (ADAM8).	[4]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Disintegrin and metalloproteinase domain-containing protein 8 (ADAM8).	[5]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Disintegrin and metalloproteinase domain-containing protein 8 (ADAM8).	[6]
Phenytoin	DMNOKBV	Approved	Phenytoin decreases the expression of Disintegrin and metalloproteinase domain-containing protein 8 (ADAM8).	[7]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Disintegrin and metalloproteinase domain-containing protein 8 (ADAM8).	[8]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Disintegrin and metalloproteinase domain-containing protein 8 (ADAM8).	[11]

References

• [1] 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.
• [2] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] 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.
• [5] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [6] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [7] Role of phenytoin in wound healing: microarray analysis of early transcriptional responses in human dermal fibroblasts. Biochem Biophys Res Commun. 2004 Feb 13;314(3):661-6. doi: 10.1016/j.bbrc.2003.12.146.
• [8] The MT1G Gene in LUHMES Neurons Is a Sensitive Biomarker of Neurotoxicity. Neurotox Res. 2020 Dec;38(4):967-978. doi: 10.1007/s12640-020-00272-3. Epub 2020 Sep 1.
• [9] 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.
• [10] 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.
• [11] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.