Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5PKX7Y)

• DOT Name: Kallikrein-11 (KLK11)
• Synonyms: hK11; EC 3.4.21.-; Hippostasin; Serine protease 20; Trypsin-like protease
• Gene Name: KLK11
• Related Disease:
  Advanced cancer
  Asthma
  Atopic dermatitis
  Benign prostatic hyperplasia
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Cardiovascular disease
  Clear cell renal carcinoma
  Epithelial ovarian cancer
  Esophageal squamous cell carcinoma
  Gastric cancer
  Graves disease
  Laryngeal carcinoma
  Lung cancer
  Lung carcinoma
  Neoplasm
  Ovarian cancer
  Ovarian neoplasm
  Prostate cancer
  Prostate carcinoma
  Prostate neoplasm
  Psoriasis
  Renal cell carcinoma
  Rhinitis
  Testicular cancer
  Laryngeal squamous cell carcinoma
  Adenoma
  Colorectal adenocarcinoma
  Colorectal neoplasm
  Mesothelioma
  Non-small-cell lung cancer
  Stomach cancer
• UniProt ID: KLK11_HUMAN
• EC Number: 3.4.21.-
• Pfam ID: PF00089
• Sequence:
  MQRLRWLRDWKSSGRGLTAAKEPGARSSPLQAMRILQLILLALATGLVGGETRIIKGFEC
  KPHSQPWQAALFEKTRLLCGATLIAPRWLLTAAHCLKPRYIVHLGQHNLQKEEGCEQTRT
  ATESFPHPGFNNSLPNKDHRNDIMLVKMASPVSITWAVRPLTLSSRCVTAGTSCLISGWG
  STSSPQLRLPHTLRCANITIIEHQKCENAYPGNITDTMVCASVQEGGKDSCQGDSGGPLV
  CNQSLQGIISWGQDPCAITRKPGVYTKVCKYVDWIQETMKNN
• Function: Possible multifunctional protease. Efficiently cleaves 'bz-Phe-Arg-4-methylcoumaryl-7-amide', a kallikrein substrate, and weakly cleaves other substrates for kallikrein and trypsin. Cleaves synthetic peptides after arginine but not lysine residues.
• Tissue Specificity: Expressed in brain, skin and prostate. Isoform 1 is expressed preferentially in brain. Isoform 2 is expressed in prostate. Present in seminal plasma at concentrations ranging from 2 to 37 microg/mL (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

33 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Asthma	DISW9QNS	Strong	Biomarker	[2]
Atopic dermatitis	DISTCP41	Strong	Altered Expression	[3]
Benign prostatic hyperplasia	DISI3CW2	Strong	Altered Expression	[4]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[5]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[6]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[7]
Cardiovascular disease	DIS2IQDX	Strong	Biomarker	[8]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[9]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[10]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[11]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[12]
Graves disease	DISU4KOQ	Strong	Biomarker	[13]
Laryngeal carcinoma	DISNHCIV	Strong	Biomarker	[14]
Lung cancer	DISCM4YA	Strong	Altered Expression	[15]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[15]
Neoplasm	DISZKGEW	Strong	Altered Expression	[16]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[10]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[10]
Prostate cancer	DISF190Y	Strong	Biomarker	[17]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[17]
Prostate neoplasm	DISHDKGQ	Strong	Genetic Variation	[18]
Psoriasis	DIS59VMN	Strong	Altered Expression	[19]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[9]
Rhinitis	DISKLMN7	Strong	Biomarker	[2]
Testicular cancer	DIS6HNYO	Strong	Biomarker	[20]
Laryngeal squamous cell carcinoma	DIS9UUVF	moderate	Biomarker	[21]
Adenoma	DIS78ZEV	Limited	Altered Expression	[10]
Colorectal adenocarcinoma	DISPQOUB	Limited	Biomarker	[22]
Colorectal neoplasm	DISR1UCN	Limited	Altered Expression	[22]
Mesothelioma	DISKWK9M	Limited	Biomarker	[23]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Biomarker	[24]
Stomach cancer	DISKIJSX	Limited	Biomarker	[25]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Kallikrein-11 (KLK11) affects the response to substance of Cisplatin.	[28]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Kallikrein-11 (KLK11).	[26]

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 Kallikrein-11 (KLK11).	[27]

References

• [1] Anionic carboxymethylagarose-based pH-responsive smart superabsorbent hydrogels for controlled release of anticancer drug.Int J Biol Macromol. 2019 Mar 1;124:1220-1229. doi: 10.1016/j.ijbiomac.2018.12.045. Epub 2018 Dec 4.
• [2] The significance of the levels of IL-4, IL-31 and TLSP in patients with asthma and/or rhinitis.Immunotherapy. 2017 Mar;9(4):331-337. doi: 10.2217/imt-2016-0131.
• [3] Osthole attenuates mouse atopic dermatitis by inhibiting thymic stromal lymphopoietin production from keratinocytes.Exp Dermatol. 2019 May;28(5):561-567. doi: 10.1111/exd.13910.
• [4] mRNA expression analysis of human kallikrein 11 (KLK11) may be useful in the discrimination of benign prostatic hyperplasia from prostate cancer after needle prostate biopsy.Biol Chem. 2006 Jun;387(6):789-93. doi: 10.1515/BC.2006.099.
• [5] Identification, Molecular Characterization and Alternative Splicing of Three Novel Members of the Canine Kallikrein (Klk)-related Peptidase Family.Anticancer Res. 2015 May;35(5):2715-23.
• [6] Bioregulation of kallikrein-related peptidases 6, 10 and 11 by the kinin B?receptor in breast cancer cells.Anticancer Res. 2014 Dec;34(12):6925-38.
• [7] Intracellular signaling pathways regulate hormone-dependent kallikrein gene expression.Tumour Biol. 2008;29(2):63-75. doi: 10.1159/000135686. Epub 2008 Jun 2.
• [8] Use of a proximity extension assay proteomics chip to discover new biomarkers associated with albuminuria.Eur J Prev Cardiol. 2017 Mar;24(4):340-348. doi: 10.1177/2047487316676134. Epub 2016 Oct 28.
• [9] Prognostic implications of the immunohistochemical expression of human kallikreins 5, 6, 10 and 11 in renal cell carcinoma.Tumour Biol. 2006;27(1):1-7. doi: 10.1159/000090150. Epub 2005 Dec 8.
• [10] Human kallikrein gene 11 (KLK11) mRNA overexpression is associated with poor prognosis in patients with epithelial ovarian cancer.Clin Cancer Res. 2004 Apr 15;10(8):2766-70. doi: 10.1158/1078-0432.ccr-03-0269.
• [11] KLK11 suppresses cellular proliferation via inhibition of Wnt/-catenin signaling pathway in esophageal squamous cell carcinoma.Am J Cancer Res. 2019 Oct 1;9(10):2264-2277. eCollection 2019.
• [12] Identification and validation of Kallikrein-ralated peptidase 11 as a novel prognostic marker of gastric cancer based on immunohistochemistry.J Surg Oncol. 2011 Oct;104(5):516-24. doi: 10.1002/jso.21981. Epub 2011 May 25.
• [13] Thymic stromal lymphopoietin gene promoter polymorphisms and expression levels in Graves' disease and Graves' ophthalmopathy.BMC Med Genet. 2012 Nov 30;13:116. doi: 10.1186/1471-2350-13-116.
• [14] Diagnostic and prognostic significance of human kallikrein 11 (KLK11) mRNA expression levels in patients with laryngeal cancer.Clin Biochem. 2012 Jun;45(9):623-30. doi: 10.1016/j.clinbiochem.2012.03.005. Epub 2012 Mar 11.
• [15] Decreased kallikrein 11 messenger RNA expression in lung cancer.Clin Lung Cancer. 2006 Jul;8(1):45-8. doi: 10.3816/CLC.2006.n.032.
• [16] Clinical relevance of kallikrein-related peptidase 9, 10, 11, and 15 mRNA expression in advanced high-grade serous ovarian cancer.PLoS One. 2017 Nov 2;12(11):e0186847. doi: 10.1371/journal.pone.0186847. eCollection 2017.
• [17] Association of TMPRSS2 and KLK11 gene expression levels with clinical progression of human prostate cancer.Med Oncol. 2010 Mar;27(1):145-51. doi: 10.1007/s12032-009-9185-0. Epub 2009 Feb 26.
• [18] Treatment of PC3 prostate cancer cells with mitoxantrone, etoposide, doxorubicin and carboplatin induces distinct alterations in the expression of kallikreins 5 and 11.Thromb Haemost. 2009 Feb;101(2):373-80.
• [19] Aberrant human tissue kallikrein levels in the stratum corneum and serum of patients with psoriasis: dependence on phenotype, severity and therapy.Br J Dermatol. 2007 May;156(5):875-83. doi: 10.1111/j.1365-2133.2006.07743.x.
• [20] Human tissue kallikrein gene family: applications in cancer.Cancer Lett. 2005 Jun 16;224(1):1-22. doi: 10.1016/j.canlet.2004.09.024.
• [21] Low mRNA expression levels of kallikrein-related peptidase 4 (KLK4) predict short-term relapse in patients with laryngeal squamous cell carcinoma.Biol Chem. 2014 Sep;395(9):1051-62. doi: 10.1515/hsz-2014-0139.
• [22] KLK11 mRNA expression predicts poor disease-free and overall survival in colorectal adenocarcinoma patients.Biomark Med. 2014;8(5):671-85. doi: 10.2217/bmm.13.151.
• [23] Global gene expression profiling of pleural mesotheliomas: overexpression of aurora kinases and P16/CDKN2A deletion as prognostic factors and critical evaluation of microarray-based prognostic prediction.Cancer Res. 2006 Mar 15;66(6):2970-9. doi: 10.1158/0008-5472.CAN-05-3907.
• [24] Is Human Kallikrein 11 in Non-small Cell Lung Cancer Treated Chemoradiotherapy Associated with Survival?.Cancer Res Treat. 2016 Jan;48(1):98-105. doi: 10.4143/crt.2014.364. Epub 2015 Mar 13.
• [25] Prognostic significance of human tissue kallikrein-related peptidases 11 and 15 in gastric cancer.Tumour Biol. 2016 Jan;37(1):437-46. doi: 10.1007/s13277-015-3802-7. Epub 2015 Jul 30.
• [26] Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells. Toxicol Appl Pharmacol. 2009 Nov 1;240(3):355-66.
• [27] 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.
• [28] 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.