Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHD8HPU)

• DOT Name: Neurexophilin-2 (NXPH2)
• Gene Name: NXPH2
• Related Disease:
  Epithelial ovarian cancer
  Ovarian cancer
  Ovarian neoplasm
• UniProt ID: NXPH2_HUMAN
• Pfam ID: PF06312
• Sequence:
  MRLRPLPLVVVPGLLQLLFCDSKEVVHATEGLDWEDKDAPGTLVGNVVHSRIISPLRLFV
  KQSPVPKPGPMAYADSMENFWDWLANITEIQEPLARTKRRPIVKTGKFKKMFGWGDFHSN
  IKTVKLNLLITGKIVDHGNGTFSVYFRHNSTGLGNVSVSLVPPSKVVEFEVSPQSTLETK
  ESKSFNCRIEYEKTDRAKKTALCNFDPSKICYQEQTQSHVSWLCSKPFKVICIYIAFYSV
  DYKLVQKVCPDYNYHSETPYLSSG
• Function: May be signaling molecules that resemble neuropeptides and that act by binding to alpha-neurexins and possibly other receptors.
• Tissue Specificity: Expressed in brain and kidney.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Epithelial ovarian cancer	DIS56MH2	moderate	Genetic Variation	[1]
Ovarian cancer	DISZJHAP	moderate	Genetic Variation	[1]
Ovarian neoplasm	DISEAFTY	moderate	Genetic Variation	[1]

6 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 Neurexophilin-2 (NXPH2).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Neurexophilin-2 (NXPH2).	[3]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Neurexophilin-2 (NXPH2).	[4]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Neurexophilin-2 (NXPH2).	[5]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Neurexophilin-2 (NXPH2).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Neurexophilin-2 (NXPH2).	[8]

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 affects the methylation of Neurexophilin-2 (NXPH2).	[7]

References

• [1] Association between invasive ovarian cancer susceptibility and 11 best candidate SNPs from breast cancer genome-wide association study.Hum Mol Genet. 2009 Jun 15;18(12):2297-304. doi: 10.1093/hmg/ddp138. Epub 2009 Mar 20.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [4] 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.
• [5] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [6] 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.
• [7] 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.
• [8] 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.