Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI858LL)

• DOT Name: NIPA-like protein 3 (NIPAL3)
• Gene Name: NIPAL3
• Related Disease:
  Prostate cancer
  Prostate neoplasm
• UniProt ID: NPAL3_HUMAN
• Pfam ID: PF05653
• Sequence:
  MDGSHSAALKLQQLPPTSSSSAVSEASFSYKENLIGALLAIFGHLVVSIALNLQKYCHIR
  LAGSKDPRAYFKTKTWWLGLFLMLLGELGVFASYAFAPLSLIVPLSAVSVIASAIIGIIF
  IKEKWKPKDFLRRYVLSFVGCGLAVVGTYLLVTFAPNSHEKMTGENVTRHLVSWPFLLYM
  LVEIILFCLLLYFYKEKNANNIVVILLLVALLGSMTVVTVKAVAGMLVLSIQGNLQLDYP
  IFYVMFVCMVATAVYQAAFLSQASQMYDSSLIASVGYILSTTIAITAGAIFYLDFIGEDV
  LHICMFALGCLIAFLGVFLITRNRKKPIPFEPYISMDAMPGMQNMHDKGMTVQPELKASF
  SYGALENNDNISEIYAPATLPVMQEEHGSRSASGVPYRVLEHTKKE
• Reactome Pathway: Miscellaneous transport and binding events (R-HSA-5223345)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Prostate cancer	DISF190Y	Strong	Biomarker	[1]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[1]

8 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 NIPA-like protein 3 (NIPAL3).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of NIPA-like protein 3 (NIPAL3).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of NIPA-like protein 3 (NIPAL3).	[4]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of NIPA-like protein 3 (NIPAL3).	[5]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of NIPA-like protein 3 (NIPAL3).	[7]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of NIPA-like protein 3 (NIPAL3).	[8]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of NIPA-like protein 3 (NIPAL3).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of NIPA-like protein 3 (NIPAL3).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of NIPA-like protein 3 (NIPAL3).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of NIPA-like protein 3 (NIPAL3).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of NIPA-like protein 3 (NIPAL3).	[6]

References

• [1] Integrative molecular concept modeling of prostate cancer progression.Nat Genet. 2007 Jan;39(1):41-51. doi: 10.1038/ng1935. Epub 2006 Dec 17.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] 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.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [6] 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.
• [7] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [10] 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.
• [11] 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.