Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTME5GRT)

• DOT Name: Alpha-ketoglutarate-dependent dioxygenase alkB homolog 6 (ALKBH6)
• Synonyms: EC 1.14.11.-; Alkylated DNA repair protein alkB homolog 6
• Gene Name: ALKBH6
• UniProt ID: ALKB6_HUMAN
• PDB ID: 7VJS; 7VJV
• EC Number: 1.14.11.-
• Pfam ID: PF13532
• Sequence:
  MEEQDARVPALEPFRVEQAPPVIYYVPDFISKEEEEYLLRQVFNAPKPKWTQLSGRKLQN
  WGGLPHPRGMVPERLPPWLQRYVDKVSNLSLFGGLPANHVLVNQYLPGEGIMPHEDGPLY
  YPTVSTISLGSHTVLDFYEPRRPEDDDPTEQPRPPPRPTTSLLLEPRSLLVLRGPAYTRL
  LHGIAAARVDALDAASSPPNAAACPSARPGACLVRGTRVSLTIRRVPRVLRAGLLLGK
• Function: Probable dioxygenase that requires molecular oxygen, alpha-ketoglutarate and iron.
• Tissue Specificity: Widely expressed, with highest expression in testis and pancreas.

Molecular Interaction Atlas (MIA) of This DOT

5 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 Alpha-ketoglutarate-dependent dioxygenase alkB homolog 6 (ALKBH6).	[1]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Alpha-ketoglutarate-dependent dioxygenase alkB homolog 6 (ALKBH6).	[2]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Alpha-ketoglutarate-dependent dioxygenase alkB homolog 6 (ALKBH6).	[3]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Alpha-ketoglutarate-dependent dioxygenase alkB homolog 6 (ALKBH6).	[5]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Alpha-ketoglutarate-dependent dioxygenase alkB homolog 6 (ALKBH6).	[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 Alpha-ketoglutarate-dependent dioxygenase alkB homolog 6 (ALKBH6).	[4]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] 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.
• [3] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [4] 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.
• [5] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [6] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.