Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2OTGGV)

• DOT Name: Neuromodulin (GAP43)
• Synonyms: Axonal membrane protein GAP-43; Growth-associated protein 43; Neural phosphoprotein B-50; pp46
• Gene Name: GAP43
• UniProt ID: NEUM_HUMAN
• Pfam ID: PF00612 ; PF06614 ; PF10580
• Sequence:
  MLCCMRRTKQVEKNDDDQKIEQDGIKPEDKAHKAATKIQASFRGHITRKKLKGEKKDDVQ
  AAEAEANKKDEAPVADGVEKKGEGTTTAEAAPATGSKPDEPGKAGETPSEEKKGEGDAAT
  EQAAPQAPASSEEKAGSAETESATKASTDNSPSSKAEDAPAKEEPKQADVPAAVTAAAAT
  TPAAEDAAAKATAQPPTETGESSQAEENIEAVDETKPKESARQDEGKEEEPEADQEHA
• Function: This protein is associated with nerve growth. It is a major component of the motile 'growth cones' that form the tips of elongating axons. Plays a role in axonal and dendritic filopodia induction.
• Reactome Pathway: L1CAM interactions (R-HSA-373760)

Molecular Interaction Atlas (MIA) of This DOT

29 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 Neuromodulin (GAP43).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Neuromodulin (GAP43).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Neuromodulin (GAP43).	[3]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Neuromodulin (GAP43).	[4]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Neuromodulin (GAP43).	[5]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Neuromodulin (GAP43).	[6]
Menadione	DMSJDTY	Approved	Menadione increases the expression of Neuromodulin (GAP43).	[7]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Neuromodulin (GAP43).	[6]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of Neuromodulin (GAP43).	[8]
Cocaine	DMSOX7I	Approved	Cocaine decreases the expression of Neuromodulin (GAP43).	[9]
Sulindac	DM2QHZU	Approved	Sulindac affects the expression of Neuromodulin (GAP43).	[10]
Lovastatin	DM9OZWQ	Approved	Lovastatin increases the expression of Neuromodulin (GAP43).	[11]
Scopolamine	DMOM8AL	Approved	Scopolamine decreases the expression of Neuromodulin (GAP43).	[12]
Meclizine	DMS7T13	Approved	Meclizine affects the expression of Neuromodulin (GAP43).	[10]
Methazolamide	DM7J2TA	Approved	Methazolamide affects the expression of Neuromodulin (GAP43).	[10]
Megestrol	DMDH9KX	Approved	Megestrol affects the expression of Neuromodulin (GAP43).	[10]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Neuromodulin (GAP43).	[6]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Neuromodulin (GAP43).	[13]
Verapamil	DMA7PEW	Phase 2/3 Trial	Verapamil affects the expression of Neuromodulin (GAP43).	[10]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Neuromodulin (GAP43).	[6]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Neuromodulin (GAP43).	[15]
AMEP	DMFELMQ	Phase 1	AMEP decreases the expression of Neuromodulin (GAP43).	[16]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Neuromodulin (GAP43).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Neuromodulin (GAP43).	[18]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Neuromodulin (GAP43).	[19]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Neuromodulin (GAP43).	[20]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of Neuromodulin (GAP43).	[16]
Paraoxon	DMN4ZKC	Investigative	Paraoxon decreases the expression of Neuromodulin (GAP43).	[21]
tryptanthrin	DMTRYCI	Investigative	tryptanthrin increases the expression of Neuromodulin (GAP43).	[22]

1 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 Neuromodulin (GAP43).	[14]

References

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• [5] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
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• [10] Discovery of molecular mechanisms of neuroprotection using cell-based bioassays and oligonucleotide arrays. Physiol Genomics. 2002 Oct 29;11(2):45-52. doi: 10.1152/physiolgenomics.00064.2002.
• [11] Lovastatin induces neuronal differentiation and apoptosis of embryonal carcinoma and neuroblastoma cells: enhanced differentiation and apoptosis in combination with dbcAMP. Mol Cell Biochem. 2010 Dec;345(1-2):1-11. doi: 10.1007/s11010-010-0553-z. Epub 2010 Aug 9.
• [12] Protective role of Ashwagandha leaf extract and its component withanone on scopolamine-induced changes in the brain and brain-derived cells. PLoS One. 2011;6(11):e27265. doi: 10.1371/journal.pone.0027265. Epub 2011 Nov 11.
• [13] Interactive gene expression pattern in prostate cancer cells exposed to phenolic antioxidants. Life Sci. 2002 Mar 1;70(15):1821-39.
• [14] 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.
• [15] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [16] Use of human neuroblastoma SH-SY5Y cells to evaluate glyphosate-induced effects on oxidative stress, neuronal development and cell death signaling pathways. Environ Int. 2020 Feb;135:105414. doi: 10.1016/j.envint.2019.105414. Epub 2019 Dec 23.
• [17] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [18] Proteomics and disease network associations evaluation of environmentally relevant Bisphenol A concentrations in a human 3D neural stem cell model. Front Cell Dev Biol. 2023 Aug 16;11:1236243. doi: 10.3389/fcell.2023.1236243. eCollection 2023.
• [19] 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.
• [20] 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.
• [21] High concentration of trichlorfon (1mM) disrupts axonal cytoskeleton and decreases the expression of plasticity-related proteins in SH-SY5Y cells. Toxicol In Vitro. 2017 Mar;39:84-92. doi: 10.1016/j.tiv.2016.12.003. Epub 2016 Dec 7.
• [22] Tryptanthrin induces growth inhibition and neuronal differentiation in the human neuroblastoma LA-N-1 cells. Chem Biol Interact. 2013 Apr 25;203(2):512-21. doi: 10.1016/j.cbi.2013.03.001. Epub 2013 Mar 13.