Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTD7GPRL)

• DOT Name: High mobility group nucleosome-binding domain-containing protein 4 (HMGN4)
• Synonyms: Non-histone chromosomal protein HMG-17-like 3; Non-histone chromosomal protein
• Gene Name: HMGN4
• Related Disease:
  Neoplasm
  Alphavirus infectious disease
  Hepatocellular carcinoma
  Thyroid cancer
  Thyroid gland carcinoma
  Thyroid tumor
• UniProt ID: HMGN4_HUMAN
• Pfam ID: PF01101
• Sequence:
  MPKRKAKGDAKGDKAKVKDEPQRRSARLSAKPAPPKPEPRPKKASAKKGEKLPKGRKGKA
  DAGKDGNNPAKNRDASTLQSQKAEGTGDAK

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Biomarker	[1]
Alphavirus infectious disease	DISZGSCJ	Strong	Biomarker	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[3]
Thyroid cancer	DIS3VLDH	Limited	Biomarker	[4]
Thyroid gland carcinoma	DISMNGZ0	Limited	Biomarker	[4]
Thyroid tumor	DISLVKMD	Limited	Altered Expression	[4]

5 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of High mobility group nucleosome-binding domain-containing protein 4 (HMGN4).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of High mobility group nucleosome-binding domain-containing protein 4 (HMGN4).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of High mobility group nucleosome-binding domain-containing protein 4 (HMGN4).	[7]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of High mobility group nucleosome-binding domain-containing protein 4 (HMGN4).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of High mobility group nucleosome-binding domain-containing protein 4 (HMGN4).	[9]

References

• [1] Arsenoplatin-1 Is a Dual Pharmacophore Anticancer Agent.J Am Chem Soc. 2019 Apr 24;141(16):6453-6457. doi: 10.1021/jacs.8b13681. Epub 2019 Apr 15.
• [2] The prophylactic and therapeutic activity of a broadly active ribonucleoside analog in a murine model of intranasal venezuelan equine encephalitis virus infection.Antiviral Res. 2019 Nov;171:104597. doi: 10.1016/j.antiviral.2019.104597. Epub 2019 Sep 5.
• [3] Identification of novel biomarkers for hepatocellular carcinoma using transcriptome analysis.J Cell Physiol. 2019 Apr;234(4):4851-4863. doi: 10.1002/jcp.27283. Epub 2018 Sep 11.
• [4] Elevated HMGN4 expression potentiates thyroid tumorigenesis.Carcinogenesis. 2017 Apr 1;38(4):391-401. doi: 10.1093/carcin/bgx015.
• [5] 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.
• [6] 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.
• [7] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] 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.