Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEU2OSU)

DOT Name	Serine protease inhibitor Kazal-type 13 (SPINK13)
Synonyms	Hepatitis B virus DNA polymerase transactivated serine protease inhibitor; Hespintor; Serine protease inhibitor Kazal-type 5-like 3
Gene Name	SPINK13
Related Disease	Epithelial ovarian cancer ( ) Hepatocellular carcinoma ( ) Neoplasm ( ) Ovarian cancer ( ) Ovarian neoplasm ( ) Clear cell renal carcinoma ( ) Renal cell carcinoma ( )
UniProt ID	ISK13_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF00050
Sequence	MAAFPHKIIFFLVCSTLTHVAFSGIFNKRDFTRWPKPRCKMYIPLDPDYNADCPNVTAPV CASNGHTFQNECFFCVEQREFHYRIKFEKYGKCD
Function	May be a serine protease inhibitor. Essential for sperm maturation and fertility. Inhibits sperm acrosome reaction, protecting sperm from premature reaction.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[1]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Altered Expression	[2]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[1]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[1]
Clear cell renal carcinoma	DISBXRFJ	Limited	Altered Expression	[3]
Renal cell carcinoma	DISQZ2X8	Limited	Altered Expression	[3]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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 Serine protease inhibitor Kazal-type 13 (SPINK13).	[4]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Serine protease inhibitor Kazal-type 13 (SPINK13).	[6]
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6 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Serine protease inhibitor Kazal-type 13 (SPINK13).	[5]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Serine protease inhibitor Kazal-type 13 (SPINK13).	[7]
Malathion	DMXZ84M	Approved	Malathion decreases the expression of Serine protease inhibitor Kazal-type 13 (SPINK13).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Serine protease inhibitor Kazal-type 13 (SPINK13).	[9]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Serine protease inhibitor Kazal-type 13 (SPINK13).	[10]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Serine protease inhibitor Kazal-type 13 (SPINK13).	[11]
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References

1	Downregulation of SPINK13 Promotes Metastasis by Regulating uPA in Ovarian Cancer Cells.Cell Physiol Biochem. 2018;45(3):1061-1071. doi: 10.1159/000487348. Epub 2018 Feb 7.
2	Novel urokinase-plasminogen activator inhibitor SPINK13 inhibits growth and metastasis of hepatocellular carcinoma in vivo.Pharmacol Res. 2019 May;143:73-85. doi: 10.1016/j.phrs.2019.03.009. Epub 2019 Mar 9.
3	The Role of Serine Peptidase Inhibitor Kazal Type 13 (SPINK13) as a Clinicopathological and Prognostic Biomarker in Patients with Clear Cell Renal Cell Carcinoma.Med Sci Monit. 2019 Dec 11;25:9458-9470. doi: 10.12659/MSM.917754.
4	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.
5	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.
6	Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
7	Effects of progesterone treatment on expression of genes involved in uterine quiescence. Reprod Sci. 2011 Aug;18(8):781-97.
8	Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
9	Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
10	Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
11	Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.