Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5NEUQE)

• DOT Name: Aldehyde dehydrogenase family 3 member B1 (ALDH3B1)
• Synonyms: EC 1.2.1.28; EC 1.2.1.5; EC 1.2.1.7; Aldehyde dehydrogenase 7
• Gene Name: ALDH3B1
• UniProt ID: AL3B1_HUMAN
• EC Number: 1.2.1.28; 1.2.1.5; 1.2.1.7
• Pfam ID: PF00171
• Sequence:
  MDPLGDTLRRLREAFHAGRTRPAEFRAAQLQGLGRFLQENKQLLHDALAQDLHKSAFESE
  VSEVAISQGEVTLALRNLRAWMKDERVPKNLATQLDSAFIRKEPFGLVLIIAPWNYPLNL
  TLVPLVGALAAGNCVVLKPSEISKNVEKILAEVLPQYVDQSCFAVVLGGPQETGQLLEHR
  FDYIFFTGSPRVGKIVMTAAAKHLTPVTLELGGKNPCYVDDNCDPQTVANRVAWFRYFNA
  GQTCVAPDYVLCSPEMQERLLPALQSTITRFYGDDPQSSPNLGRIINQKQFQRLRALLGC
  GRVAIGGQSDESDRYIAPTVLVDVQEMEPVMQEEIFGPILPIVNVQSLDEAIEFINRREK
  PLALYAFSNSSQVVKRVLTQTSSGGFCGNDGFMHMTLASLPFGGVGASGMGRYHGKFSFD
  TFSHHRACLLRSPGMEKLNALRYPPQSPRRLRMLLVAMEAQGCSCTLL
• Function: Oxidizes medium and long chain saturated and unsaturated aldehydes. Metabolizes also benzaldehyde. Low activity towards acetaldehyde and 3,4-dihydroxyphenylacetaldehyde. May not metabolize short chain aldehydes. Can use both NADP(+) and NAD(+) as electron acceptor. May have a protective role against the cytotoxicity induced by lipid peroxidation.
• Tissue Specificity: Highest expression in kidney and lung.
• KEGG Pathway:
  Glycolysis / Gluconeogenesis (hsa00010)
  Histidine metabolism (hsa00340)
  Tyrosine metabolism (hsa00350)
  Phenylalanine metabolism (hsa00360)
  beta-Alanine metabolism (hsa00410)
  Metabolism of xenobiotics by cytochrome P450 (hsa00980)
  Drug metabolism - cytochrome P450 (hsa00982)
  Metabolic pathways (hsa01100)
• Reactome Pathway:
  Neutrophil degranulation (R-HSA-6798695)
  Sphingolipid metabolism (R-HSA-428157)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 4 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Aldehyde dehydrogenase family 3 member B1 (ALDH3B1) decreases the response to substance of Arsenic trioxide.	[19]
Hydrogen peroxide	DM1NG5W	Approved	Aldehyde dehydrogenase family 3 member B1 (ALDH3B1) decreases the response to substance of Hydrogen peroxide.	[18]
Menadione	DMSJDTY	Approved	Aldehyde dehydrogenase family 3 member B1 (ALDH3B1) decreases the response to substance of Menadione.	[18]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	Aldehyde dehydrogenase family 3 member B1 (ALDH3B1) decreases the response to substance of 4-hydroxy-2-nonenal.	[18]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Aldehyde dehydrogenase family 3 member B1 (ALDH3B1).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the methylation of Aldehyde dehydrogenase family 3 member B1 (ALDH3B1).	[2]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Aldehyde dehydrogenase family 3 member B1 (ALDH3B1).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Aldehyde dehydrogenase family 3 member B1 (ALDH3B1).	[13]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Aldehyde dehydrogenase family 3 member B1 (ALDH3B1).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Aldehyde dehydrogenase family 3 member B1 (ALDH3B1).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Aldehyde dehydrogenase family 3 member B1 (ALDH3B1).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Aldehyde dehydrogenase family 3 member B1 (ALDH3B1).	[5]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Aldehyde dehydrogenase family 3 member B1 (ALDH3B1).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Aldehyde dehydrogenase family 3 member B1 (ALDH3B1).	[7]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Aldehyde dehydrogenase family 3 member B1 (ALDH3B1).	[8]
Beta-carotene	DM0RXBT	Approved	Beta-carotene decreases the expression of Aldehyde dehydrogenase family 3 member B1 (ALDH3B1).	[10]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Aldehyde dehydrogenase family 3 member B1 (ALDH3B1).	[11]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of Aldehyde dehydrogenase family 3 member B1 (ALDH3B1).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Aldehyde dehydrogenase family 3 member B1 (ALDH3B1).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Aldehyde dehydrogenase family 3 member B1 (ALDH3B1).	[16]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde decreases the expression of Aldehyde dehydrogenase family 3 member B1 (ALDH3B1).	[17]

2 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Octanal	DMTN0OK	Investigative	Octanal affects the binding of Aldehyde dehydrogenase family 3 member B1 (ALDH3B1).	[18]
Nitrophenyl acetate	DMHSD8A	Investigative	Nitrophenyl acetate affects the binding of Aldehyde dehydrogenase family 3 member B1 (ALDH3B1).	[18]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [3] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [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] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [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] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [9] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [10] Beta-carotene and apocarotenals promote retinoid signaling in BEAS-2B human bronchioepithelial cells. Arch Biochem Biophys. 2006 Nov 1;455(1):48-60.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [13] 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.
• [14] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [15] 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.
• [16] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [17] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
• [18] Molecular characterization, expression analysis, and role of ALDH3B1 in the cellular protection against oxidative stress. Free Radic Biol Med. 2010 Nov 15;49(9):1432-43. doi: 10.1016/j.freeradbiomed.2010.08.004. Epub 2010 Aug 10.
• [19] 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.