Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTD573EL)

DOT Name	Kallikrein-10 (KLK10)
Synonyms	EC 3.4.21.-; Normal epithelial cell-specific 1; Protease serine-like 1
Gene Name	KLK10
Related Disease	Breast neoplasm ( ) Epithelial ovarian cancer ( ) Matthew-Wood syndrome ( ) Alzheimer disease ( ) Breast cancer ( ) Breast carcinoma ( ) Carcinoma of esophagus ( ) Cervical cancer ( ) Cervical carcinoma ( ) Clear cell renal carcinoma ( ) Colorectal carcinoma ( ) Dementia ( ) Digestive system neoplasm ( ) Esophageal cancer ( ) Gastric cancer ( ) Hepatitis B virus infection ( ) Hepatitis C virus infection ( ) Hepatocellular carcinoma ( ) Hereditary diffuse gastric adenocarcinoma ( ) Liver cirrhosis ( ) Multiple sclerosis ( ) Neoplasm ( ) Neoplasm of esophagus ( ) Nervous system inflammation ( ) Pituitary gland disorder ( ) Prostate carcinoma ( ) Prostate neoplasm ( ) Renal cell carcinoma ( ) Squamous cell carcinoma ( ) Stomach cancer ( ) Thyroid gland papillary carcinoma ( ) Adenocarcinoma ( ) Ductal breast carcinoma in situ ( ) Gastric neoplasm ( ) Pancreatic ductal carcinoma ( ) Non-small-cell lung cancer ( ) Ovarian cancer ( ) Ovarian neoplasm ( ) Pancreatic cancer ( ) Prostate cancer ( )
UniProt ID	KLK10_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	5LPE; 5LPF
EC Number	3.4.21.-
Pfam ID	PF00089
Sequence	MRAPHLHLSAASGARALAKLLPLLMAQLWAAEAALLPQNDTRLDPEAYGSPCARGSQPWQ VSLFNGLSFHCAGVLVDQSWVLTAAHCGNKPLWARVGDDHLLLLQGEQLRRTTRSVVHPK YHQGSGPILPRRTDEHDLMLLKLARPVVLGPRVRALQLPYRCAQPGDQCQVAGWGTTAAR RVKYNKGLTCSSITILSPKECEVFYPGVVTNNMICAGLDRGQDPCQSDSGGPLVCDETLQ GILSWGVYPCGSAQHPAVYTQICKYMSWINKVIRSN
Function	Has a tumor-suppressor role for NES1 in breast and prostate cancer.
Tissue Specificity	Expressed in breast, ovary and prostate.

Molecular Interaction Atlas (MIA) of This DOT

40 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Breast neoplasm	DISNGJLM	Definitive	Biomarker	[1]
Epithelial ovarian cancer	DIS56MH2	Definitive	Biomarker	[2]
Matthew-Wood syndrome	DISA7HR7	Definitive	Biomarker	[3]
Alzheimer disease	DISF8S70	Strong	Altered Expression	[4]
Breast cancer	DIS7DPX1	Strong	Biomarker	[5]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[5]
Carcinoma of esophagus	DISS6G4D	Strong	Biomarker	[6]
Cervical cancer	DISFSHPF	Strong	Biomarker	[7]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[7]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[8]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[2]
Dementia	DISXL1WY	Strong	Biomarker	[9]
Digestive system neoplasm	DISPOJCT	Strong	Altered Expression	[6]
Esophageal cancer	DISGB2VN	Strong	Biomarker	[6]
Gastric cancer	DISXGOUK	Strong	Biomarker	[10]
Hepatitis B virus infection	DISLQ2XY	Strong	Genetic Variation	[11]
Hepatitis C virus infection	DISQ0M8R	Strong	Posttranslational Modification	[11]
Hepatocellular carcinoma	DIS0J828	Strong	Posttranslational Modification	[11]
Hereditary diffuse gastric adenocarcinoma	DISUIBYS	Strong	Biomarker	[12]
Liver cirrhosis	DIS4G1GX	Strong	Posttranslational Modification	[11]
Multiple sclerosis	DISB2WZI	Strong	Biomarker	[13]
Neoplasm	DISZKGEW	Strong	Altered Expression	[14]
Neoplasm of esophagus	DISOLKAQ	Strong	Biomarker	[6]
Nervous system inflammation	DISB3X5A	Strong	Biomarker	[13]
Pituitary gland disorder	DIS7XB48	Strong	Altered Expression	[15]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[16]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[17]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[8]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[18]
Stomach cancer	DISKIJSX	Strong	Biomarker	[10]
Thyroid gland papillary carcinoma	DIS48YMM	Strong	Altered Expression	[19]
Adenocarcinoma	DIS3IHTY	moderate	Altered Expression	[20]
Ductal breast carcinoma in situ	DISLCJY7	moderate	Altered Expression	[21]
Gastric neoplasm	DISOKN4Y	moderate	Altered Expression	[12]
Pancreatic ductal carcinoma	DIS26F9Q	moderate	Altered Expression	[20]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Biomarker	[22]
Ovarian cancer	DISZJHAP	Limited	Biomarker	[2]
Ovarian neoplasm	DISEAFTY	Limited	Posttranslational Modification	[23]
Pancreatic cancer	DISJC981	Limited	Altered Expression	[24]
Prostate cancer	DISF190Y	Limited	Altered Expression	[16]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Kallikrein-10 (KLK10) affects the response to substance of Cisplatin.	[37]
Captopril	DM458UM	Approved	Kallikrein-10 (KLK10) increases the Blood pressure decreased ADR of Captopril.	[38]
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11 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Kallikrein-10 (KLK10).	[25]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Kallikrein-10 (KLK10).	[26]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Kallikrein-10 (KLK10).	[27]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Kallikrein-10 (KLK10).	[28]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Kallikrein-10 (KLK10).	[29]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Kallikrein-10 (KLK10).	[30]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate decreases the expression of Kallikrein-10 (KLK10).	[31]
Alitretinoin	DMME8LH	Approved	Alitretinoin increases the expression of Kallikrein-10 (KLK10).	[32]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Kallikrein-10 (KLK10).	[33]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Kallikrein-10 (KLK10).	[35]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Kallikrein-10 (KLK10).	[36]
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⏷ Show the Full List of 11 Drug(s)

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 Kallikrein-10 (KLK10).	[34]
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References

1	Kallikrein 10 (KLK10) methylation as a novel prognostic biomarker in early breast cancer.Ann Oncol. 2009 Jun;20(6):1020-5. doi: 10.1093/annonc/mdn733. Epub 2009 Jan 15.
2	Clinical significance of kallikrein-related peptidase (KLK10) mRNA expression in colorectal cancer.Clin Biochem. 2013 Oct;46(15):1453-61. doi: 10.1016/j.clinbiochem.2013.03.002. Epub 2013 Mar 13.
3	Aberrant upregulation of KLK10 promotes metastasis via enhancement of EMT and FAK/SRC/ERK axis in PDAC.Biochem Biophys Res Commun. 2018 May 15;499(3):584-593. doi: 10.1016/j.bbrc.2018.03.194. Epub 2018 Apr 4.
4	Kallikrein-related peptidases 6 and 10 are elevated in cerebrospinal fluid of patients with Alzheimer's disease and associated with CSF-TAU and FDG-PET.Transl Neurodegener. 2019 Aug 27;8:25. doi: 10.1186/s40035-019-0168-6. eCollection 2019.
5	Identification of KLK10 as a therapeutic target to reverse trastuzumab resistance in breast cancer.Oncotarget. 2016 Nov 29;7(48):79494-79502. doi: 10.18632/oncotarget.13104.
6	Upregulated KLK10 inhibits esophageal cancer proliferation and enhances cisplatin sensitivity invitro.Oncol Rep. 2015 Nov;34(5):2325-32. doi: 10.3892/or.2015.4211. Epub 2015 Aug 20.
7	MiR-199b-5p promotes tumor growth and metastasis in cervical cancer by down-regulating KLK10.Biochem Biophys Res Commun. 2018 Sep 5;503(2):556-563. doi: 10.1016/j.bbrc.2018.05.165. Epub 2018 Aug 2.
8	Dysregulation of kallikrein-related peptidases in renal cell carcinoma: potential targets of miRNAs.Biol Chem. 2010 Apr;391(4):411-23. doi: 10.1515/BC.2010.041.
9	Altered kallikrein 7 and 10 concentrations in cerebrospinal fluid of patients with Alzheimer's disease and frontotemporal dementia.Clin Biochem. 2004 Mar;37(3):230-7. doi: 10.1016/j.clinbiochem.2003.11.012.
10	NES1/KLK10 promotes trastuzumab resistance via activation of PI3K/AKT signaling pathway in gastric cancer.J Cell Biochem. 2018 Aug;119(8):6398-6407. doi: 10.1002/jcb.26562. Epub 2018 Apr 17.
11	Aberrant DNA methylation profile and frequent methylation of KLK10 and OXGR1 genes in hepatocellular carcinoma.Genes Chromosomes Cancer. 2009 Dec;48(12):1057-68. doi: 10.1002/gcc.20708.
12	Downregulation and CpG island hypermethylation of NES1/hK10 gene in the pathogenesis of human gastric cancer.Cancer Lett. 2007 Jun 18;251(1):78-85. doi: 10.1016/j.canlet.2006.11.006. Epub 2006 Dec 19.
13	Differential expression of multiple kallikreins in a viral model of multiple sclerosis points to unique roles in the innate and adaptive immune response.Biol Chem. 2014 Sep;395(9):1063-73. doi: 10.1515/hsz-2014-0141.
14	NES1/KLK10 and hNIS gene therapy enhanced iodine-131 internal radiation in PC3 proliferation inhibition.Front Med. 2019 Dec;13(6):646-657. doi: 10.1007/s11684-018-0643-y. Epub 2019 May 22.
15	Human kallikrein 10 expression in surgically removed human pituitary corticotroph adenomas: an immunohistochemical study.Appl Immunohistochem Mol Morphol. 2015 Jul;23(6):433-7. doi: 10.1097/PAI.0000000000000108.
16	NES1/KLK10 gene represses proliferation, enhances apoptosis and down-regulates glucose metabolism of PC3 prostate cancer cells.Sci Rep. 2015 Nov 30;5:17426. doi: 10.1038/srep17426.
17	Downregulation of human kallikrein 10 (KLK10/NES1) by CpG island hypermethylation in breast, ovarian and prostate cancers.Tumour Biol. 2005 Nov-Dec;26(6):324-36. doi: 10.1159/000089290. Epub 2005 Oct 26.
18	Expression of the human kallikrein genes 10 (KLK10) and 11 (KLK11) in cancerous and non-cancerous lung tissues.Biol Chem. 2006 Jun;387(6):783-8. doi: 10.1515/BC.2006.098.
19	Gene expression profiling identifies potential molecular markers of papillary thyroid carcinoma.Cancer Biomark. 2019;24(1):71-83. doi: 10.3233/CBM-181758.
20	Co-expression of KLK6 and KLK10 as prognostic factors for survival in pancreatic ductal adenocarcinoma.Br J Cancer. 2008 Nov 4;99(9):1484-92. doi: 10.1038/sj.bjc.6604717. Epub 2008 Oct 14.
21	Loss of expression of the putative tumor suppressor NES1 gene in biopsy-proven ductal carcinoma in situ predicts for invasive carcinoma at definitive surgery.Int J Radiat Oncol Biol Phys. 2003 Jul 1;56(3):653-7. doi: 10.1016/s0360-3016(03)00068-3.
22	Methylation of multiple genes as a candidate biomarker in non-small cell lung cancer.Cancer Lett. 2011 Apr 1;303(1):21-8. doi: 10.1016/j.canlet.2010.12.011. Epub 2011 Jan 20.
23	KLK10 exon 3 unmethylated PCR product concentration: a new potential early diagnostic marker in ovarian cancer? - A pilot study.J Ovarian Res. 2018 Apr 24;11(1):32. doi: 10.1186/s13048-018-0407-y.
24	In-silico analysis of kallikrein gene expression in pancreatic and colon cancers.Anticancer Res. 2004 Jan-Feb;24(1):43-51.
25	Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
26	Effect of retinoic acid on gene expression in human conjunctival epithelium: secretory phospholipase A2 mediates retinoic acid induction of MUC16. Invest Ophthalmol Vis Sci. 2005 Nov;46(11):4050-61.
27	Kallikrein-related peptidase 10 (KLK10) expression and single nucleotide polymorphisms in ovarian cancer survival. Int J Gynecol Cancer. 2010 May;20(4):529-36. doi: 10.1111/IGC.0b013e3181d9273e.
28	Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
29	Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
30	Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
31	CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
32	The human kallikrein 10 promoter contains a functional retinoid response element. Biol Chem. 2006 Jun;387(6):741-7. doi: 10.1515/BC.2006.093.
33	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.
34	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.
35	CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
36	Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
37	Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.
38	ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.