Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTX9UREP)

• DOT Name: NIPA-like protein 2 (NIPAL2)
• Gene Name: NIPAL2
• UniProt ID: NPAL2_HUMAN
• Pfam ID: PF05653
• Sequence:
  MAAVAPAGPGDSASAALDELSLNFTYGAPGAGNGSLSGDWYRRNQIHLFGVLLAILGNLV
  ISISLNIQKYSHLQLAQQEHPRPYFKSVLWWGGVLLMAVGETGNFAAYGFAPITLIAPLG
  CVSVTGSAIISVTFLKDNLRASDLLGTTLAFAGTYLLVNFAPNITQAISARTVQYYLVGW
  QFLIYVILEILIFCILLYFYKRKGMKHMVILLTLVAILASLTVISVKAVSGMITFSVMDK
  MQLTYPIFYIMFIIMIASCVFQVKFLNQATKLYNTTTVVPVNHIFFTISAIIAGIIFYQE
  FLGAPFLTVFIYLFGCFLSFLGVFLVTRNREKEHLQQSYIDFGNIPGKQMLDKIQPDSHS
  LSYGTLPDGSDSTKSQSGEKKEV
• Reactome Pathway: Miscellaneous transport and binding events (R-HSA-5223345)

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
Chlorothiazide	DMLHESP	Approved	NIPA-like protein 2 (NIPAL2) increases the Metabolic disorder ADR of Chlorothiazide.	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of NIPA-like protein 2 (NIPAL2).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of NIPA-like protein 2 (NIPAL2).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of NIPA-like protein 2 (NIPAL2).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of NIPA-like protein 2 (NIPAL2).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of NIPA-like protein 2 (NIPAL2).	[4]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of NIPA-like protein 2 (NIPAL2).	[5]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of NIPA-like protein 2 (NIPAL2).	[6]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of NIPA-like protein 2 (NIPAL2).	[7]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of NIPA-like protein 2 (NIPAL2).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of NIPA-like protein 2 (NIPAL2).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of NIPA-like protein 2 (NIPAL2).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of NIPA-like protein 2 (NIPAL2).	[12]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of NIPA-like protein 2 (NIPAL2).	[13]

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] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [3] 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.
• [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 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.
• [6] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [7] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [8] 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.
• [9] 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.
• [10] BET bromodomain inhibition targets both c-Myc and IL7R in high-risk acute lymphoblastic leukemia. Blood. 2012 Oct 4;120(14):2843-52.
• [11] Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.
• [12] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [13] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [14] Genome-wide association analyses suggest NELL1 influences adverse metabolic response to HCTZ in African Americans. Pharmacogenomics J. 2014 Feb;14(1):35-40. doi: 10.1038/tpj.2013.3. Epub 2013 Feb 12.