Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHF4LKX)

• DOT Name: PLAC8-like protein 1 (PLAC8L1)
• Gene Name: PLAC8L1
• Related Disease: Acute myelogenous leukaemia
• UniProt ID: PL8L1_HUMAN
• Pfam ID: PF04749
• Sequence:
  MNWFGSNFFRCPEDLSLLNIYSPLLSHMSSEDEHFISNLRGHVPASAVVKQPVRGASGRT
  TITAIVQTGGGWSTGLFSVCRDRRICFCGLFCPMCLECDIARHYGECLCWPLLPGSTFAL
  RIGTRERHKIQGTLCEDWLAVHCCWAFSICQVARELKMRTSQVYEICAVPMTKDTLV

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of PLAC8-like protein 1 (PLAC8L1).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of PLAC8-like protein 1 (PLAC8L1).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of PLAC8-like protein 1 (PLAC8L1).	[4]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of PLAC8-like protein 1 (PLAC8L1).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of PLAC8-like protein 1 (PLAC8L1).	[6]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of PLAC8-like protein 1 (PLAC8L1).	[7]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of PLAC8-like protein 1 (PLAC8L1).	[9]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of PLAC8-like protein 1 (PLAC8L1).	[10]

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 decreases the methylation of PLAC8-like protein 1 (PLAC8L1).	[8]

References

• [1] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [2] 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.
• [3] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [6] 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.
• [7] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [8] 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.
• [9] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [10] Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.