Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTY4LG3Z)

• DOT Name: Haloacid dehalogenase-like hydrolase domain-containing protein 3 (HDHD3)
• Gene Name: HDHD3
• UniProt ID: HDHD3_HUMAN
• PDB ID: 3K1Z
• Pfam ID: PF00702
• Sequence:
  MAHRLQIRLLTWDVKDTLLRLRHPLGEAYATKARAHGLEVEPSALEQGFRQAYRAQSHSF
  PNYGLSHGLTSRQWWLDVVLQTFHLAGVQDAQAVAPIAEQLYKDFSHPCTWQVLDGAEDT
  LRECRTRGLRLAVISNFDRRLEGILGGLGLREHFDFVLTSEAAGWPKPDPRIFQEALRLA
  HMEPVVAAHVGDNYLCDYQGPRAVGMHSFLVVGPQALDPVVRDSVPKEHILPSLAHLLPA
  LDCLEGSTPGL

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Haloacid dehalogenase-like hydrolase domain-containing protein 3 (HDHD3) decreases the response to substance of Arsenic trioxide.	[12]

12 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 Haloacid dehalogenase-like hydrolase domain-containing protein 3 (HDHD3).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Haloacid dehalogenase-like hydrolase domain-containing protein 3 (HDHD3).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Haloacid dehalogenase-like hydrolase domain-containing protein 3 (HDHD3).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Haloacid dehalogenase-like hydrolase domain-containing protein 3 (HDHD3).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Haloacid dehalogenase-like hydrolase domain-containing protein 3 (HDHD3).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Haloacid dehalogenase-like hydrolase domain-containing protein 3 (HDHD3).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Haloacid dehalogenase-like hydrolase domain-containing protein 3 (HDHD3).	[8]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Haloacid dehalogenase-like hydrolase domain-containing protein 3 (HDHD3).	[6]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Haloacid dehalogenase-like hydrolase domain-containing protein 3 (HDHD3).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Haloacid dehalogenase-like hydrolase domain-containing protein 3 (HDHD3).	[2]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Haloacid dehalogenase-like hydrolase domain-containing protein 3 (HDHD3).	[10]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Haloacid dehalogenase-like hydrolase domain-containing protein 3 (HDHD3).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Haloacid dehalogenase-like hydrolase domain-containing protein 3 (HDHD3).	[7]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [7] Epigenetic changes in individuals with arsenicosis. Chem Res Toxicol. 2011 Feb 18;24(2):165-7. doi: 10.1021/tx1004419. Epub 2011 Feb 4.
• [8] 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.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [11] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [12] The NRF2-mediated oxidative stress response pathway is associated with tumor cell resistance to arsenic trioxide across the NCI-60 panel. BMC Med Genomics. 2010 Aug 13;3:37. doi: 10.1186/1755-8794-3-37.