Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNE0XHQ)

• DOT Name: Claudin-7 (CLDN7)
• Synonyms: CLDN-7
• Gene Name: CLDN7
• Related Disease:
  B-cell neoplasm
  Carcinoma of liver and intrahepatic biliary tract
  Liver cancer
  Lung adenocarcinoma
  Rheumatoid arthritis
  Arteriosclerosis
  Atherosclerosis
  Atopic dermatitis
  Breast cancer
  Breast carcinoma
  Colon cancer
  Colon carcinoma
  Colonic neoplasm
  Colorectal carcinoma
  Colorectal neoplasm
  Diabetic retinopathy
  Endometrial cancer
  Endometrial carcinoma
  Endometriosis
  Eosinophilic esophagitis
  Esophageal squamous cell carcinoma
  Hepatitis C virus infection
  Hepatocellular carcinoma
  Laryngeal carcinoma
  Neonatal ichthyosis-sclerosing cholangitis syndrome
  Ovarian neoplasm
  Pancreatic cancer
  Prostate cancer
  Renal cell carcinoma
  Stroke
  Triple negative breast cancer
  Carcinoma
  High blood pressure
  Non-small-cell lung cancer
  Prostate carcinoma
  Squamous cell carcinoma
  Stomach cancer
  Adenoma
  Autosomal dominant polycystic kidney disease
  Breast neoplasm
  Clear cell renal carcinoma
  Colitis
  Epithelial ovarian cancer
  Gastric cancer
  Metastatic malignant neoplasm
  Nasopharyngeal carcinoma
  Prostate neoplasm
  Ulcerative colitis
• UniProt ID: CLD7_HUMAN
• Pfam ID: PF00822
• Sequence:
  MANSGLQLLGFSMALLGWVGLVACTAIPQWQMSSYAGDNIITAQAMYKGLWMDCVTQSTG
  MMSCKMYDSVLALSAALQATRALMVVSLVLGFLAMFVATMGMKCTRCGGDDKVKKARIAM
  GGGIIFIVAGLAALVACSWYGHQIVTDFYNPLIPTNIKYEFGPAIFIGWAGSALVILGGA
  LLSCSCPGNESKAGYRVPRSYPKSNSSKEYV
• Function: Plays a major role in tight junction-specific obliteration of the intercellular space.
• Tissue Specificity: Expressed in kidney, lung and prostate. Isoform 1 seems to be predominant, except in some normal prostate samples, where isoform 2 is the major form. Down-regulated in breast cancers, including ductal carcinoma in situ (DCIS), lobular carcinoma in situ (LCIS) and invasive ductal carcinoma (IDC) (at protein level), as well as in several cancer cell lines. Loss of expression correlates with histological grade, occurring predominantly in high-grade lesions.
• KEGG Pathway:
  Cell adhesion molecules (hsa04514)
  Tight junction (hsa04530)
  Leukocyte transendothelial migration (hsa04670)
  Pathogenic Escherichia coli infection (hsa05130)
  Hepatitis C (hsa05160)
• Reactome Pathway: Tight junction interactions (R-HSA-420029)

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
B-cell neoplasm	DISVY326	Definitive	Altered Expression	[1]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Definitive	Biomarker	[2]
Liver cancer	DISDE4BI	Definitive	Biomarker	[2]
Lung adenocarcinoma	DISD51WR	Definitive	Biomarker	[3]
Rheumatoid arthritis	DISTSB4J	Definitive	Altered Expression	[4]
Arteriosclerosis	DISK5QGC	Strong	Altered Expression	[5]
Atherosclerosis	DISMN9J3	Strong	Altered Expression	[5]
Atopic dermatitis	DISTCP41	Strong	Biomarker	[6]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[7]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[7]
Colon cancer	DISVC52G	Strong	Biomarker	[8]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[9]
Colonic neoplasm	DISSZ04P	Strong	Altered Expression	[10]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[11]
Colorectal neoplasm	DISR1UCN	Strong	Biomarker	[9]
Diabetic retinopathy	DISHGUJM	Strong	Altered Expression	[12]
Endometrial cancer	DISW0LMR	Strong	Biomarker	[13]
Endometrial carcinoma	DISXR5CY	Strong	Biomarker	[13]
Endometriosis	DISX1AG8	Strong	Biomarker	[14]
Eosinophilic esophagitis	DISR8WSB	Strong	Altered Expression	[15]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[16]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[17]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[18]
Laryngeal carcinoma	DISNHCIV	Strong	Biomarker	[19]
Neonatal ichthyosis-sclerosing cholangitis syndrome	DISFCNXC	Strong	Biomarker	[20]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[21]
Pancreatic cancer	DISJC981	Strong	Altered Expression	[22]
Prostate cancer	DISF190Y	Strong	Altered Expression	[23]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[24]
Stroke	DISX6UHX	Strong	Biomarker	[25]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[26]
Carcinoma	DISH9F1N	moderate	Altered Expression	[27]
High blood pressure	DISY2OHH	moderate	Altered Expression	[28]
Non-small-cell lung cancer	DIS5Y6R9	moderate	Biomarker	[29]
Prostate carcinoma	DISMJPLE	moderate	Altered Expression	[23]
Squamous cell carcinoma	DISQVIFL	moderate	Biomarker	[30]
Stomach cancer	DISKIJSX	moderate	Biomarker	[31]
Adenoma	DIS78ZEV	Limited	Biomarker	[11]
Autosomal dominant polycystic kidney disease	DISBHWUI	Limited	Altered Expression	[32]
Breast neoplasm	DISNGJLM	Limited	Biomarker	[33]
Clear cell renal carcinoma	DISBXRFJ	Limited	Altered Expression	[34]
Colitis	DISAF7DD	Limited	Altered Expression	[35]
Epithelial ovarian cancer	DIS56MH2	Limited	Biomarker	[36]
Gastric cancer	DISXGOUK	Limited	Biomarker	[31]
Metastatic malignant neoplasm	DIS86UK6	Limited	Altered Expression	[37]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Biomarker	[38]
Prostate neoplasm	DISHDKGQ	Limited	Biomarker	[39]
Ulcerative colitis	DIS8K27O	Limited	Biomarker	[40]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Claudin-7 (CLDN7) decreases the response to substance of Arsenic trioxide.	[60]

20 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 Claudin-7 (CLDN7).	[41]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Claudin-7 (CLDN7).	[42]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Claudin-7 (CLDN7).	[43]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Claudin-7 (CLDN7).	[44]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Claudin-7 (CLDN7).	[45]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Claudin-7 (CLDN7).	[46]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Claudin-7 (CLDN7).	[47]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Claudin-7 (CLDN7).	[48]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Claudin-7 (CLDN7).	[49]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Claudin-7 (CLDN7).	[50]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Claudin-7 (CLDN7).	[51]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Claudin-7 (CLDN7).	[52]
Azacitidine	DMTA5OE	Approved	Azacitidine decreases the expression of Claudin-7 (CLDN7).	[53]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Claudin-7 (CLDN7).	[50]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Claudin-7 (CLDN7).	[50]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Claudin-7 (CLDN7).	[55]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Claudin-7 (CLDN7).	[56]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Claudin-7 (CLDN7).	[57]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Claudin-7 (CLDN7).	[58]
Okadaic acid	DM47CO1	Investigative	Okadaic acid increases the expression of Claudin-7 (CLDN7).	[59]

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 Claudin-7 (CLDN7).	[54]

References

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