Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNUHAC1)

• DOT Name: Neural cell adhesion molecule 1 (NCAM1)
• Synonyms: N-CAM-1; NCAM-1; CD antigen CD56
• Gene Name: NCAM1
• UniProt ID: NCAM1_HUMAN
• PDB ID: 2E3V; 2HAZ; 2VKW; 2VKX; 3MTR; 5AEA; 5LKN
• Pfam ID: PF00041 ; PF07679 ; PF13927
• Sequence:
  MLQTKDLIWTLFFLGTAVSLQVDIVPSQGEISVGESKFFLCQVAGDAKDKDISWFSPNGE
  KLTPNQQRISVVWNDDSSSTLTIYNANIDDAGIYKCVVTGEDGSESEATVNVKIFQKLMF
  KNAPTPQEFREGEDAVIVCDVVSSLPPTIIWKHKGRDVILKKDVRFIVLSNNYLQIRGIK
  KTDEGTYRCEGRILARGEINFKDIQVIVNVPPTIQARQNIVNATANLGQSVTLVCDAEGF
  PEPTMSWTKDGEQIEQEEDDEKYIFSDDSSQLTIKKVDKNDEAEYICIAENKAGEQDATI
  HLKVFAKPKITYVENQTAMELEEQVTLTCEASGDPIPSITWRTSTRNISSEEKASWTRPE
  KQETLDGHMVVRSHARVSSLTLKSIQYTDAGEYICTASNTIGQDSQSMYLEVQYAPKLQG
  PVAVYTWEGNQVNITCEVFAYPSATISWFRDGQLLPSSNYSNIKIYNTPSASYLEVTPDS
  ENDFGNYNCTAVNRIGQESLEFILVQADTPSSPSIDQVEPYSSTAQVQFDEPEATGGVPI
  LKYKAEWRAVGEEVWHSKWYDAKEASMEGIVTIVGLKPETTYAVRLAALNGKGLGEISAA
  SEFKTQPVQGEPSAPKLEGQMGEDGNSIKVNLIKQDDGGSPIRHYLVRYRALSSEWKPEI
  RLPSGSDHVMLKSLDWNAEYEVYVVAENQQGKSKAAHFVFRTSAQPTAIPANGSPTSGLS
  TGAIVGILIVIFVLLLVVVDITCYFLNKCGLFMCIAVNLCGKAGPGAKGKDMEEGKAAFS
  KDESKEPIVEVRTEEERTPNHDGGKHTEPNETTPLTEPEKGPVEAKPECQETETKPAPAE
  VKTVPNDATQTKENESKA
• Function: This protein is a cell adhesion molecule involved in neuron-neuron adhesion, neurite fasciculation, outgrowth of neurites, etc.; (Microbial infection) Acts as a receptor for rabies virus; (Microbial infection) Acts as a receptor for Zika virus.
• KEGG Pathway:
  Virion - Ebolavirus and Lyssavirus (hsa03265)
  Cell adhesion molecules (hsa04514)
  Prion disease (hsa05020)
• Reactome Pathway:
  NCAM signaling for neurite out-growth (R-HSA-375165)
  NCAM1 interactions (R-HSA-419037)
  Signal transduction by L1 (R-HSA-445144)
  RAF/MAP kinase cascade (R-HSA-5673001)
  Interferon gamma signaling (R-HSA-877300)
  ECM proteoglycans (R-HSA-3000178)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Camptothecin	DM6CHNJ	Phase 3	Neural cell adhesion molecule 1 (NCAM1) decreases the response to substance of Camptothecin.	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Neural cell adhesion molecule 1 (NCAM1).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Neural cell adhesion molecule 1 (NCAM1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Neural cell adhesion molecule 1 (NCAM1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Neural cell adhesion molecule 1 (NCAM1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Neural cell adhesion molecule 1 (NCAM1).	[5]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Neural cell adhesion molecule 1 (NCAM1).	[6]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Neural cell adhesion molecule 1 (NCAM1).	[7]
Folic acid	DMEMBJC	Approved	Folic acid affects the expression of Neural cell adhesion molecule 1 (NCAM1).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Neural cell adhesion molecule 1 (NCAM1).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Neural cell adhesion molecule 1 (NCAM1).	[13]
Paraquat	DMR8O3X	Investigative	Paraquat decreases the expression of Neural cell adhesion molecule 1 (NCAM1).	[14]
Chlorpyrifos	DMKPUI6	Investigative	Chlorpyrifos decreases the expression of Neural cell adhesion molecule 1 (NCAM1).	[15]

2 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate affects the localization of Neural cell adhesion molecule 1 (NCAM1).	[9]
Tributylstannanyl	DMHN7CB	Investigative	Tributylstannanyl affects the localization of Neural cell adhesion molecule 1 (NCAM1).	[9]

2 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 Neural cell adhesion molecule 1 (NCAM1).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the methylation of Neural cell adhesion molecule 1 (NCAM1).	[12]

References

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• [2] Evaluation of a human iPSC-derived BBB model for repeated dose toxicity testing with cyclosporine A as model compound. Toxicol In Vitro. 2021 Jun;73:105112. doi: 10.1016/j.tiv.2021.105112. Epub 2021 Feb 22.
• [3] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [4] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [5] 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.
• [6] Drinking-water arsenic exposure modulates gene expression in human lymphocytes from a U.S. population. Environ Health Perspect. 2008 Apr;116(4):524-31. doi: 10.1289/ehp.10861.
• [7] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [8] Effects of folate deficiency on gene expression in the apoptosis and cancer pathways in colon cancer cells. Carcinogenesis. 2006 May;27(5):916-24. doi: 10.1093/carcin/bgi312. Epub 2005 Dec 16.
• [9] Activation of p44/42 in human natural killer cells decreases cell-surface protein expression: Relationship to tributyltin-induced alterations of protein expression. Toxicol Mech Methods. 2010 Nov;20(9):544-55. doi: 10.3109/15376516.2010.518174. Epub 2010 Sep 30.
• [10] 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.
• [11] 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.
• [12] 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.
• [13] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [14] An in vitro strategy using multiple human induced pluripotent stem cell-derived models to assess the toxicity of chemicals: A case study on paraquat. Toxicol In Vitro. 2022 Jun;81:105333. doi: 10.1016/j.tiv.2022.105333. Epub 2022 Feb 16.
• [15] Chlorpyrifos inhibits neural induction via Mfn1-mediated mitochondrial dysfunction in human induced pluripotent stem cells. Sci Rep. 2017 Jan 23;7:40925. doi: 10.1038/srep40925.
• [16] ATR inhibitors VE-821 and VX-970 sensitize cancer cells to topoisomerase i inhibitors by disabling DNA replication initiation and fork elongation responses. Cancer Res. 2014 Dec 1;74(23):6968-79.