Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNWAQ4Y)

DOT Name Neural cell adhesion molecule L1 (L1CAM)
Synonyms N-CAM-L1; NCAM-L1; CD antigen CD171
Gene Name L1CAM
Related Disease
L1 syndrome ( )
MASA syndrome ( )
X-linked complicated corpus callosum dysgenesis ( )
X-linked hydrocephalus with stenosis of the aqueduct of Sylvius ( )
X-linked complicated spastic paraplegia type 1 ( )
UniProt ID
L1CAM_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
8AFO; 8AFP
Pfam ID
PF13882 ; PF00041 ; PF07679 ; PF13927
Sequence
MVVALRYVWPLLLCSPCLLIQIPEEYEGHHVMEPPVITEQSPRRLVVFPTDDISLKCEAS
GKPEVQFRWTRDGVHFKPKEELGVTVYQSPHSGSFTITGNNSNFAQRFQGIYRCFASNKL
GTAMSHEIRLMAEGAPKWPKETVKPVEVEEGESVVLPCNPPPSAEPLRIYWMNSKILHIK
QDERVTMGQNGNLYFANVLTSDNHSDYICHAHFPGTRTIIQKEPIDLRVKATNSMIDRKP
RLLFPTNSSSHLVALQGQPLVLECIAEGFPTPTIKWLRPSGPMPADRVTYQNHNKTLQLL
KVGEEDDGEYRCLAENSLGSARHAYYVTVEAAPYWLHKPQSHLYGPGETARLDCQVQGRP
QPEVTWRINGIPVEELAKDQKYRIQRGALILSNVQPSDTMVTQCEARNRHGLLLANAYIY
VVQLPAKILTADNQTYMAVQGSTAYLLCKAFGAPVPSVQWLDEDGTTVLQDERFFPYANG
TLGIRDLQANDTGRYFCLAANDQNNVTIMANLKVKDATQITQGPRSTIEKKGSRVTFTCQ
ASFDPSLQPSITWRGDGRDLQELGDSDKYFIEDGRLVIHSLDYSDQGNYSCVASTELDVV
ESRAQLLVVGSPGPVPRLVLSDLHLLTQSQVRVSWSPAEDHNAPIEKYDIEFEDKEMAPE
KWYSLGKVPGNQTSTTLKLSPYVHYTFRVTAINKYGPGEPSPVSETVVTPEAAPEKNPVD
VKGEGNETTNMVITWKPLRWMDWNAPQVQYRVQWRPQGTRGPWQEQIVSDPFLVVSNTST
FVPYEIKVQAVNSQGKGPEPQVTIGYSGEDYPQAIPELEGIEILNSSAVLVKWRPVDLAQ
VKGHLRGYNVTYWREGSQRKHSKRHIHKDHVVVPANTTSVILSGLRPYSSYHLEVQAFNG
RGSGPASEFTFSTPEGVPGHPEALHLECQSNTSLLLRWQPPLSHNGVLTGYVLSYHPLDE
GGKGQLSFNLRDPELRTHNLTDLSPHLRYRFQLQATTKEGPGEAIVREGGTMALSGISDF
GNISATAGENYSVVSWVPKEGQCNFRFHILFKALGEEKGGASLSPQYVSYNQSSYTQWDL
QPDTDYEIHLFKERMFRHQMAVKTNGTGRVRLPPAGFATEGWFIGFVSAIILLLLVLLIL
CFIKRSKGGKYSVKDKEDTQVDSEARPMKDETFGEYRSLESDNEEKAFGSSQPSLNGDIK
PLGSDDSLADYGGSVDVQFNEDGSFIGQYSGKKEKEAAGGNDSSGATSPINPAVALE
Function
Neural cell adhesion molecule involved in the dynamics of cell adhesion and in the generation of transmembrane signals at tyrosine kinase receptors. During brain development, critical in multiple processes, including neuronal migration, axonal growth and fasciculation, and synaptogenesis. In the mature brain, plays a role in the dynamics of neuronal structure and function, including synaptic plasticity.
KEGG Pathway
Axon guidance (hsa04360 )
Cell adhesion molecules (hsa04514 )
Reactome Pathway
L1CAM interactions (R-HSA-373760 )
Recycling pathway of L1 (R-HSA-437239 )
Interaction between L1 and Ankyrins (R-HSA-445095 )
Signal transduction by L1 (R-HSA-445144 )
Basigin interactions (R-HSA-210991 )

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
L1 syndrome DISYPSZE Definitive X-linked [1]
MASA syndrome DISEFI9B Definitive X-linked recessive [2]
X-linked complicated corpus callosum dysgenesis DIS1L185 Definitive X-linked recessive [3]
X-linked hydrocephalus with stenosis of the aqueduct of Sylvius DIS6QXIR Definitive X-linked [4]
X-linked complicated spastic paraplegia type 1 DISUKJK8 Supportive X-linked [5]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 2 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Mitomycin DMH0ZJE Approved Neural cell adhesion molecule L1 (L1CAM) affects the response to substance of Mitomycin. [26]
Rapamycin Immunosuppressant Drug DM678IB Investigative Neural cell adhesion molecule L1 (L1CAM) affects the response to substance of Rapamycin Immunosuppressant Drug. [27]
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23 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 Neural cell adhesion molecule L1 (L1CAM). [6]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Neural cell adhesion molecule L1 (L1CAM). [7]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Neural cell adhesion molecule L1 (L1CAM). [6]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Neural cell adhesion molecule L1 (L1CAM). [8]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Neural cell adhesion molecule L1 (L1CAM). [9]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Neural cell adhesion molecule L1 (L1CAM). [10]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Neural cell adhesion molecule L1 (L1CAM). [11]
Vorinostat DMWMPD4 Approved Vorinostat increases the expression of Neural cell adhesion molecule L1 (L1CAM). [12]
Triclosan DMZUR4N Approved Triclosan increases the expression of Neural cell adhesion molecule L1 (L1CAM). [13]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Neural cell adhesion molecule L1 (L1CAM). [14]
Progesterone DMUY35B Approved Progesterone decreases the expression of Neural cell adhesion molecule L1 (L1CAM). [15]
Fluorouracil DMUM7HZ Approved Fluorouracil decreases the expression of Neural cell adhesion molecule L1 (L1CAM). [16]
Panobinostat DM58WKG Approved Panobinostat increases the expression of Neural cell adhesion molecule L1 (L1CAM). [12]
Fulvestrant DM0YZC6 Approved Fulvestrant increases the expression of Neural cell adhesion molecule L1 (L1CAM). [17]
Ethanol DMDRQZU Approved Ethanol decreases the activity of Neural cell adhesion molecule L1 (L1CAM). [18]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of Neural cell adhesion molecule L1 (L1CAM). [12]
Genistein DM0JETC Phase 2/3 Genistein decreases the expression of Neural cell adhesion molecule L1 (L1CAM). [10]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Neural cell adhesion molecule L1 (L1CAM). [21]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Neural cell adhesion molecule L1 (L1CAM). [10]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Neural cell adhesion molecule L1 (L1CAM). [22]
Coumestrol DM40TBU Investigative Coumestrol decreases the expression of Neural cell adhesion molecule L1 (L1CAM). [23]
Acetaldehyde DMJFKG4 Investigative Acetaldehyde increases the expression of Neural cell adhesion molecule L1 (L1CAM). [24]
Deguelin DMXT7WG Investigative Deguelin decreases the expression of Neural cell adhesion molecule L1 (L1CAM). [25]
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⏷ Show the Full List of 23 Drug(s)
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Saracatinib DMBLHGP Phase 2 Saracatinib decreases the phosphorylation of Neural cell adhesion molecule L1 (L1CAM). [19]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Neural cell adhesion molecule L1 (L1CAM). [20]
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References

1 Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
2 MASA syndrome is due to mutations in the neural cell adhesion gene L1CAM. Nat Genet. 1994 Jul;7(3):408-13. doi: 10.1038/ng0794-408.
3 [X-linked hereditary spastic paraplegia due to mutation in the L1CAM gene: three cases reports of CRASH syndrome]. Rev Neurol. 2016 Mar 1;62(5):218-22.
4 Hereditary stenosis of the aqueduct of Sylvius as a cause of congenital hydrocephalus. Brain. 1949 Jun;72(Pt. 2):246-62. doi: 10.1093/brain/72.2.246.
5 L1 Syndrome. 2004 Apr 28 [updated 2021 Jan 7]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
6 Neuronal and cardiac toxicity of pharmacological compounds identified through transcriptomic analysis of human pluripotent stem cell-derived embryoid bodies. Toxicol Appl Pharmacol. 2021 Dec 15;433:115792. doi: 10.1016/j.taap.2021.115792. Epub 2021 Nov 3.
7 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
8 Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
9 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
10 Convergent transcriptional profiles induced by endogenous estrogen and distinct xenoestrogens in breast cancer cells. Carcinogenesis. 2006 Aug;27(8):1567-78.
11 Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
12 A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
13 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
14 Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
15 Coordinate up-regulation of TMEM97 and cholesterol biosynthesis genes in normal ovarian surface epithelial cells treated with progesterone: implications for pathogenesis of ovarian cancer. BMC Cancer. 2007 Dec 11;7:223.
16 Dissecting progressive stages of 5-fluorouracil resistance in vitro using RNA expression profiling. Int J Cancer. 2004 Nov 1;112(2):200-12. doi: 10.1002/ijc.20401.
17 Arsenite and cadmium promote the development of mammary tumors. Carcinogenesis. 2020 Jul 14;41(7):1005-1014. doi: 10.1093/carcin/bgz176.
18 Alcohol inhibits cell-cell adhesion mediated by human L1. J Cell Biol. 1996 Apr;133(2):381-90. doi: 10.1083/jcb.133.2.381.
19 L1 coupling to ankyrin and the spectrin-actin cytoskeleton modulates ethanol inhibition of L1 adhesion and ethanol teratogenesis. FASEB J. 2018 Mar;32(3):1364-1374. doi: 10.1096/fj.201700970. Epub 2018 Jan 3.
20 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.
21 The BET bromodomain inhibitor JQ1 suppresses growth of pancreatic ductal adenocarcinoma in patient-derived xenograft models. Oncogene. 2016 Feb 18;35(7):833-45.
22 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.
23 Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
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.
25 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.
26 Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.
27 L1-CAM expression in ccRCC correlates with shorter patients survival times and confers chemoresistance in renal cell carcinoma cells. Carcinogenesis. 2011 Mar;32(3):262-70. doi: 10.1093/carcin/bgq249. Epub 2010 Nov 19.