Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSWJD7B)

• DOT Name: Apelin (APLN)
• Synonyms: APJ endogenous ligand
• Gene Name: APLN
• UniProt ID: APEL_HUMAN
• Pfam ID: PF15360
• Sequence:
  MNLRLCVQALLLLWLSLTAVCGGSLMPLPDGNGLEDGNVRHLVQPRGSRNGPGPWQGGRR
  KFRRQRPRLSHKGPMPF
• Function: Endogenous ligand for the apelin receptor (APLNR). Drives internalization of the apelin receptor. Apelin-36 dissociates more hardly than (pyroglu)apelin-13 from APLNR. Hormone involved in the regulation of cardiac precursor cell movements during gastrulation and heart morphogenesis. Has an inhibitory effect on cytokine production in response to T-cell receptor/CD3 cross-linking; the oral intake of apelin in the colostrum and the milk might therefore modulate immune responses in neonates. Plays a role in early coronary blood vessels formation. Mediates myocardial contractility in an ERK1/2-dependent manner. May also have a role in the central control of body fluid homeostasis by influencing vasopressin release and drinking behavior; (Microbial infection) Endogenous ligand for the apelin receptor (APLNR), an alternative coreceptor with CD4 for HIV-1 infection. Inhibits HIV-1 entry in cells coexpressing CD4 and APLNR. Apelin-36 has a greater inhibitory activity on HIV infection than other synthetic apelin derivatives.
• Tissue Specificity: Expressed in the brain with highest levels in the frontal cortex, thalamus, hypothalamus and midbrain . Secreted by the mammary gland into the colostrum and the milk.
• KEGG Pathway:
  Neuroactive ligand-receptor interaction (hsa04080)
  Apelin sig.ling pathway (hsa04371)
• Reactome Pathway:
  G alpha (i) signalling events (R-HSA-418594)
  Peptide ligand-binding receptors (R-HSA-375276)

Molecular Interaction Atlas (MIA) of This DOT

8 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 Apelin (APLN).	[1]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Apelin (APLN).	[2]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Apelin (APLN).	[3]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Apelin (APLN).	[4]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Apelin (APLN).	[5]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Apelin (APLN).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Apelin (APLN).	[2]
Paraquat	DMR8O3X	Investigative	Paraquat decreases the expression of Apelin (APLN).	[6]

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 Apelin (APLN).	[7]

References

• [1] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [2] Genome-Wide Analysis of Low Dose Bisphenol-A (BPA) Exposure in Human Prostate Cells. Curr Genomics. 2019 May;20(4):260-274. doi: 10.2174/1389202920666190603123040.
• [3] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [4] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [5] Dexamethasone and the inflammatory response in explants of human omental adipose tissue. Mol Cell Endocrinol. 2010 Feb 5;315(1-2):292-8.
• [6] 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.
• [7] 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.