Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT16PTBC)

• DOT Name: Hepatoma-derived growth factor (HDGF)
• Synonyms: HDGF; High mobility group protein 1-like 2; HMG-1L2
• Gene Name: HDGF
• UniProt ID: HDGF_HUMAN
• PDB ID: 1RI0; 2NLU
• Pfam ID: PF00855
• Sequence:
  MSRSNRQKEYKCGDLVFAKMKGYPHWPARIDEMPEAAVKSTANKYQVFFFGTHETAFLGP
  KDLFPYEESKEKFGKPNKRKGFSEGLWEIENNPTVKASGYQSSQKKSCVEEPEPEPEAAE
  GDGDKKGNAEGSSDEEGKLVIDEPAKEKNEKGALKRRAGDLLEDSPKRPKEAENPEGEEK
  EAATLEVERPLPMEVEKNSTPSEPGSGRGPPQEEEEEEDEEEEATKEDAEAPGIRDHESL
• Function: [Isoform 1]: Acts as a transcriptional repressor. Has mitogenic activity for fibroblasts. Heparin-binding protein ; [Isoform 2]: Does not have mitogenic activity for fibroblasts. Does not bind heparin ; [Isoform 3]: Has mitogenic activity for fibroblasts. Heparin-binding protein.
• Tissue Specificity: Ubiquitous.
• Reactome Pathway: XBP1(S) activates chaperone genes (R-HSA-381038)

Molecular Interaction Atlas (MIA) of This DOT

16 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 Hepatoma-derived growth factor (HDGF).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Hepatoma-derived growth factor (HDGF).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Hepatoma-derived growth factor (HDGF).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Hepatoma-derived growth factor (HDGF).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Hepatoma-derived growth factor (HDGF).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Hepatoma-derived growth factor (HDGF).	[6]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Hepatoma-derived growth factor (HDGF).	[8]
Selenium	DM25CGV	Approved	Selenium increases the expression of Hepatoma-derived growth factor (HDGF).	[9]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Hepatoma-derived growth factor (HDGF).	[10]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of Hepatoma-derived growth factor (HDGF).	[11]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Hepatoma-derived growth factor (HDGF).	[12]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Hepatoma-derived growth factor (HDGF).	[13]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene increases the expression of Hepatoma-derived growth factor (HDGF).	[5]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Hepatoma-derived growth factor (HDGF).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Hepatoma-derived growth factor (HDGF).	[16]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Hepatoma-derived growth factor (HDGF).	[17]

4 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Quercetin	DM3NC4M	Approved	Quercetin increases the phosphorylation of Hepatoma-derived growth factor (HDGF).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Hepatoma-derived growth factor (HDGF).	[14]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Hepatoma-derived growth factor (HDGF).	[7]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid decreases the phosphorylation of Hepatoma-derived growth factor (HDGF).	[18]

References

• [1] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [2] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [3] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [4] 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.
• [5] Gene expression profiles with activation of the estrogen receptor alpha-selective estrogen receptor modulator complex in breast cancer cells expressing wild-type estrogen receptor. Cancer Res. 2002 Aug 1;62(15):4419-26.
• [6] 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.
• [7] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [8] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [9] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [10] Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
• [11] Expression profile analysis of human peripheral blood mononuclear cells in response to aspirin. Arch Immunol Ther Exp (Warsz). 2005 Mar-Apr;53(2):151-8.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [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] The genome-wide expression profile of Scrophularia ningpoensis-treated thapsigargin-stimulated U-87MG cells. Neurotoxicology. 2009 May;30(3):368-76.
• [16] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [17] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [18] Functional lipidomics: Palmitic acid impairs hepatocellular carcinoma development by modulating membrane fluidity and glucose metabolism. Hepatology. 2017 Aug;66(2):432-448. doi: 10.1002/hep.29033. Epub 2017 Jun 16.