Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTW25XLK)

• DOT Name: Galanin-like peptide (GALP)
• Gene Name: GALP
• Related Disease:
  Hyperglycemia
  Ganglioneuroblastoma
  Neuroblastic tumor
  Obesity
  Non-insulin dependent diabetes
• UniProt ID: GALP_HUMAN
• Pfam ID: PF01296
• Sequence:
  MAPPSVPLVLLLVLLLSLAETPASAPAHRGRGGWTLNSAGYLLGPVLHLPQMGDQDGKRE
  TALEILDLWKAIDGLPYSHPPQPSKRNVMETFAKPEIGDLGMLSMKIPKEEDVLKS
• Function: [Isoform 1]: Hypothalamic neuropeptide which binds to the G-protein-coupled galanin receptors (GALR1, GALR2 and GALR3). Involved in a large number of putative physiological functions in CNS homeostatic processes, including the regulation of gonadotropin-releasing hormone secretion.; [Isoform 2]: Exhibits potent and dose-dependent vasoconstrictor and anti-edema activity in the cutaneous microvasculature, a physiologic effects which does not appear to be mediated via GALR1 or GALR2. Exhibits antimicrobial activity against Gram-negative bacterias, inducing bacterial membrane blebbing.
• Tissue Specificity: Isoform 2 is found in ganglia of ganglioneuroma and ganglioneuroblastoma, as well as in differentiated tumor cells of neuroblastoma tissues. Not found in undifferentiated neuroblasts. Isoform 2 is found in the skin, in pericytes covering microvascular arterioles and venules on their abluminal surfaces. In larger vessels, isoform 2 is expressed in layers of smooth muscle cells. Isoform 2 is not detected in endothelial cells.
• KEGG Pathway: Neuroactive ligand-receptor interaction (hsa04080)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hyperglycemia	DIS0BZB5	Definitive	Altered Expression	[1]
Ganglioneuroblastoma	DIS6FPB6	Strong	Biomarker	[2]
Neuroblastic tumor	DISKWPS1	Strong	Altered Expression	[2]
Obesity	DIS47Y1K	Strong	Biomarker	[3]
Non-insulin dependent diabetes	DISK1O5Z	Disputed	Biomarker	[4]

4 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 Galanin-like peptide (GALP).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Galanin-like peptide (GALP).	[6]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Galanin-like peptide (GALP).	[7]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Galanin-like peptide (GALP).	[9]

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 decreases the methylation of Galanin-like peptide (GALP).	[8]

References

• [1] High Circulating Alarin Levels Are Associated with Presence of Metabolic Syndrome.Cell Physiol Biochem. 2018;51(5):2041-2051. doi: 10.1159/000495823. Epub 2018 Dec 6.
• [2] Gangliocytes in neuroblastic tumors express alarin, a novel peptide derived by differential splicing of the galanin-like peptide gene.J Mol Neurosci. 2006;29(2):145-52. doi: 10.1385/JMN:29:2:145.
• [3] Regulation of Feeding Behavior and Energy Metabolism by Galanin-like Peptide (GALP): A Novel Strategy to Fight Against Obesity.Curr Pharm Des. 2018;24(33):3926-3933. doi: 10.2174/1381612824666181106111623.
• [4] Circulating alarin concentrations are high in patients with type 2 diabetes and increased by glucagon-like peptide-1 receptor agonist treatment: An Consort-compliant study.Medicine (Baltimore). 2019 Jul;98(28):e16428. doi: 10.1097/MD.0000000000016428.
• [5] Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
• [6] 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.
• [7] 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.
• [8] 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.
• [9] 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.