Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9EV2XK)

• DOT Name: Cadherin-17 (CDH17)
• Synonyms: Intestinal peptide-associated transporter HPT-1; Liver-intestine cadherin; LI-cadherin
• Gene Name: CDH17
• Related Disease:
  Melanoma
  Adenocarcinoma
  Adenoma
  Barrett esophagus
  Bipolar disorder
  Breast cancer
  Breast carcinoma
  Colitis
  Colon cancer
  Colon carcinoma
  Colorectal neoplasm
  Digestive system neoplasm
  Esophageal adenocarcinoma
  Gastric adenocarcinoma
  Hepatitis B virus infection
  Hepatocellular carcinoma
  Liver cancer
  Matthew-Wood syndrome
  Metastatic malignant neoplasm
  Multiple sclerosis
  Precancerous condition
  Psychotic disorder
  Retinoblastoma
  Secondary hyperparathyroidism
  Severe combined immunodeficiency
  Thyroid gland carcinoma
  Carcinoma
  Advanced cancer
  Asthma
  Colorectal adenocarcinoma
  Colorectal carcinoma
  Gastric cancer
  Neoplasm of esophagus
  Pancreatic cancer
  Stomach cancer
• UniProt ID: CAD17_HUMAN
• PDB ID: 6ULM; 7CYM; 7EV1
• Pfam ID: PF00028
• Sequence:
  MILQAHLHSLCLLMLYLATGYGQEGKFSGPLKPMTFSIYEGQEPSQIIFQFKANPPAVTF
  ELTGETDNIFVIEREGLLYYNRALDRETRSTHNLQVAALDANGIIVEGPVPITIKVKDIN
  DNRPTFLQSKYEGSVRQNSRPGKPFLYVNATDLDDPATPNGQLYYQIVIQLPMINNVMYF
  QINNKTGAISLTREGSQELNPAKNPSYNLVISVKDMGGQSENSFSDTTSVDIIVTENIWK
  APKPVEMVENSTDPHPIKITQVRWNDPGAQYSLVDKEKLPRFPFSIDQEGDIYVTQPLDR
  EEKDAYVFYAVAKDEYGKPLSYPLEIHVKVKDINDNPPTCPSPVTVFEVQENERLGNSIG
  TLTAHDRDEENTANSFLNYRIVEQTPKLPMDGLFLIQTYAGMLQLAKQSLKKQDTPQYNL
  TIEVSDKDFKTLCFVQINVIDINDQIPIFEKSDYGNLTLAEDTNIGSTILTIQATDADEP
  FTGSSKILYHIIKGDSEGRLGVDTDPHTNTGYVIIKKPLDFETAAVSNIVFKAENPEPLV
  FGVKYNASSFAKFTLIVTDVNEAPQFSQHVFQAKVSEDVAIGTKVGNVTAKDPEGLDISY
  SLRGDTRGWLKIDHVTGEIFSVAPLDREAGSPYRVQVVATEVGGSSLSSVSEFHLILMDV
  NDNPPRLAKDYTGLFFCHPLSAPGSLIFEATDDDQHLFRGPHFTFSLGSGSLQNDWEVSK
  INGTHARLSTRHTEFEEREYVVLIRINDGGRPPLEGIVSLPVTFCSCVEGSCFRPAGHQT
  GIPTVGMAVGILLTTLLVIGIILAVVFIRIKKDKGKDNVESAQASEVKPLRS
• Function: Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types. LI-cadherin may have a role in the morphological organization of liver and intestine. Involved in intestinal peptide transport.
• Tissue Specificity: Expressed in the gastrointestinal tract and pancreatic duct. Not detected in kidney, lung, liver, brain, adrenal gland and skin.
• KEGG Pathway: Gastric cancer (hsa05226)
• Reactome Pathway: Adherens junctions interactions (R-HSA-418990)

Molecular Interaction Atlas (MIA) of This DOT

35 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Melanoma	DIS1RRCY	Definitive	Biomarker	[1]
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[2]
Adenoma	DIS78ZEV	Strong	Biomarker	[3]
Barrett esophagus	DIS416Y7	Strong	Altered Expression	[4]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[5]
Breast cancer	DIS7DPX1	Strong	Biomarker	[6]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[6]
Colitis	DISAF7DD	Strong	Biomarker	[7]
Colon cancer	DISVC52G	Strong	Altered Expression	[8]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[8]
Colorectal neoplasm	DISR1UCN	Strong	Biomarker	[9]
Digestive system neoplasm	DISPOJCT	Strong	Biomarker	[10]
Esophageal adenocarcinoma	DISODWFP	Strong	Biomarker	[11]
Gastric adenocarcinoma	DISWWLTC	Strong	Biomarker	[12]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[13]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[14]
Liver cancer	DISDE4BI	Strong	Altered Expression	[15]
Matthew-Wood syndrome	DISA7HR7	Strong	Biomarker	[16]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[17]
Multiple sclerosis	DISB2WZI	Strong	Genetic Variation	[18]
Precancerous condition	DISV06FL	Strong	Altered Expression	[15]
Psychotic disorder	DIS4UQOT	Strong	Biomarker	[19]
Retinoblastoma	DISVPNPB	Strong	Biomarker	[15]
Secondary hyperparathyroidism	DISZX24B	Strong	Biomarker	[3]
Severe combined immunodeficiency	DIS6MF4Q	Strong	Genetic Variation	[20]
Thyroid gland carcinoma	DISMNGZ0	Strong	Altered Expression	[21]
Carcinoma	DISH9F1N	moderate	Altered Expression	[22]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[23]
Asthma	DISW9QNS	Limited	Genetic Variation	[24]
Colorectal adenocarcinoma	DISPQOUB	Limited	Biomarker	[25]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[26]
Gastric cancer	DISXGOUK	Limited	Altered Expression	[2]
Neoplasm of esophagus	DISOLKAQ	Limited	Genetic Variation	[27]
Pancreatic cancer	DISJC981	Limited	Biomarker	[28]
Stomach cancer	DISKIJSX	Limited	Altered Expression	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Cadherin-17 (CDH17).	[29]
Cocaine	DMSOX7I	Approved	Cocaine decreases the expression of Cadherin-17 (CDH17).	[30]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Cadherin-17 (CDH17).	[31]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Cadherin-17 (CDH17).	[33]

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 increases the methylation of Cadherin-17 (CDH17).	[32]

References

• [1] Monoclonal Antibodies Directed against Cadherin RGD Exhibit Therapeutic Activity against Melanoma and Colorectal Cancer Metastasis.Clin Cancer Res. 2018 Jan 15;24(2):433-444. doi: 10.1158/1078-0432.CCR-17-1444. Epub 2017 Sep 15.
• [2] (111)In-labeled anti-cadherin17 antibody D2101 has potential as a noninvasive imaging probe for diagnosing gastric cancer and lymph-node metastasis.Ann Nucl Med. 2020 Jan;34(1):13-23. doi: 10.1007/s12149-019-01408-y. Epub 2019 Oct 12.
• [3] Identification of Differential Transcriptional Patterns in Primary and Secondary Hyperparathyroidism.J Clin Endocrinol Metab. 2018 Jun 1;103(6):2189-2198. doi: 10.1210/jc.2017-02506.
• [4] FABP1 and Hepar expression levels in Barrett's esophagus and associated neoplasia in an Asian population.Dig Liver Dis. 2017 Oct;49(10):1104-1109. doi: 10.1016/j.dld.2017.06.014. Epub 2017 Jul 27.
• [5] Genetic variation of the FAT gene at 4q35 is associated with bipolar affective disorder.Mol Psychiatry. 2008 Mar;13(3):277-84. doi: 10.1038/sj.mp.4002111. Epub 2007 Oct 16.
• [6] Expression of Cadherin-17 Promotes Metastasis in a Highly Bone Marrow Metastatic Murine Breast Cancer Model.Biomed Res Int. 2017;2017:8494286. doi: 10.1155/2017/8494286. Epub 2017 Jan 19.
• [7] Deletion of cadherin-17 enhances intestinal permeability andsusceptibility to intestinal tumour formation.J Pathol. 2018 Nov;246(3):289-299. doi: 10.1002/path.5138. Epub 2018 Sep 25.
• [8] Down-regulation of liver-intestine cadherin enhances noscapine-induced apoptosis in human colon cancer cells.Expert Rev Anticancer Ther. 2017 Sep;17(9):857-863. doi: 10.1080/14737140.2017.1344097. Epub 2017 Jun 27.
• [9] Determination of Cadherin-17 in Tumor Tissues of Different Metastatic Grade Using a Single Incubation-Step Amperometric Immunosensor.Anal Chem. 2018 Sep 18;90(18):11161-11167. doi: 10.1021/acs.analchem.8b03506. Epub 2018 Sep 6.
• [10] CDH17 Is a More Sensitive Marker for Gastric Adenocarcinoma Than CK20 and CDX2.Arch Pathol Lab Med. 2017 Jan;141(1):144-150. doi: 10.5858/arpa.2015-0404-OA.
• [11] Liver-intestine-cadherin is a sensitive marker of intestinal differentiation during Barrett's carcinogenesis.Dig Dis Sci. 2013 Mar;58(3):699-705. doi: 10.1007/s10620-012-2425-8. Epub 2012 Oct 4.
• [12] CDX2 co-localizes with liver-intestine cadherin in intestinal metaplasia and adenocarcinoma of the stomach.J Pathol. 2005 Apr;205(5):615-22. doi: 10.1002/path.1741.
• [13] Liver-intestine cadherin predicts microvascular invasion and poor prognosis of hepatitis B virus-positive hepatocellular carcinoma.Cancer. 2009 Oct 15;115(20):4753-65. doi: 10.1002/cncr.24513.
• [14] Cadherin 17 is related to recurrence and poor prognosis of cytokeratin 19-positive hepatocellular carcinoma.Oncol Lett. 2018 Jan;15(1):559-567. doi: 10.3892/ol.2017.7320. Epub 2017 Nov 1.
• [15] Targeting cadherin-17 inactivates Wnt signaling and inhibits tumor growth in liver carcinoma.Hepatology. 2009 Nov;50(5):1453-63. doi: 10.1002/hep.23143.
• [16] Identification and Validation of Novel Subtype-Specific Protein Biomarkers in Pancreatic Ductal Adenocarcinoma.Pancreas. 2017 Mar;46(3):311-322. doi: 10.1097/MPA.0000000000000743.
• [17] Knockdown of liver-intestine cadherin decreases BGC823 cell invasiveness and metastasis in vivo.World J Gastroenterol. 2012 Jun 28;18(24):3129-37. doi: 10.3748/wjg.v18.i24.3129.
• [18] Correlation of geographic distributions of haptoglobin alleles with prevalence of multiple sclerosis (MS) - a narrative literature review.Metab Brain Dis. 2017 Feb;32(1):19-34. doi: 10.1007/s11011-016-9923-x. Epub 2016 Nov 2.
• [19] Olanzapine-induced methylation alters cadherin gene families and associated pathways implicated in psychosis.BMC Neurosci. 2014 Sep 29;15:112. doi: 10.1186/1471-2202-15-112.
• [20] Cadherin 17 mutation associated with leaky severe combined immune deficiency is corrected by HSCT.Blood Adv. 2017 Oct 23;1(23):2083-2087. doi: 10.1182/bloodadvances.2017010926. eCollection 2017 Oct 24.
• [21] An essential role for Pax8 in the transcriptional regulation of cadherin-16 in thyroid cells.Mol Endocrinol. 2012 Jan;26(1):67-78. doi: 10.1210/me.2011-1090. Epub 2011 Dec 1.
• [22] Targeting CDH17 suppresses tumor progression in gastric cancer by downregulating Wnt/-catenin signaling.PLoS One. 2013;8(3):e56959. doi: 10.1371/journal.pone.0056959. Epub 2013 Mar 15.
• [23] RGD cadherins and 21 integrin in cancer metastasis: A dangerous liaison.Biochim Biophys Acta Rev Cancer. 2018 Apr;1869(2):321-332. doi: 10.1016/j.bbcan.2018.04.005. Epub 2018 Apr 17.
• [24] Genome-Wide Association Study Identifies Novel Loci Associated With Diisocyanate-Induced Occupational Asthma.Toxicol Sci. 2015 Jul;146(1):192-201. doi: 10.1093/toxsci/kfv084. Epub 2015 Apr 26.
• [25] Combination of cadherin-17 and SATB homeobox 2 serves as potential optimal makers for the differential diagnosis of pulmonary enteric adenocarcinoma and metastatic colorectal adenocarcinoma.Oncotarget. 2017 Jun 28;8(38):63442-63452. doi: 10.18632/oncotarget.18828. eCollection 2017 Sep 8.
• [26] Silencing of cadherin-17 enhances apoptosis and inhibits autophagy in colorectal cancer cells.Biomed Pharmacother. 2018 Dec;108:331-337. doi: 10.1016/j.biopha.2018.09.020. Epub 2018 Sep 15.
• [27] Genome-wide association analyses of esophageal squamous cell carcinoma in Chinese identify multiple susceptibility loci and gene-environment interactions.Nat Genet. 2012 Oct;44(10):1090-7. doi: 10.1038/ng.2411. Epub 2012 Sep 9.
• [28] Disruption of oncogenic liver-intestine cadherin (CDH17) drives apoptotic pancreatic cancer death.Cancer Lett. 2019 Jul 10;454:204-214. doi: 10.1016/j.canlet.2019.04.022. Epub 2019 Apr 17.
• [29] 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.
• [30] Transcriptional profiling in the human prefrontal cortex: evidence for two activational states associated with cocaine abuse. Pharmacogenomics J. 2003;3(1):27-40.
• [31] Gene-expression profiling during curcumin-induced apoptosis reveals downregulation of CXCR4. Exp Hematol. 2007 Jan;35(1):84-95.
• [32] 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.
• [33] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.