Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT27KV99)

• DOT Name: Claudin-1 (CLDN1)
• Synonyms: Senescence-associated epithelial membrane protein
• Gene Name: CLDN1
• Related Disease:
  Anal intraepithelial neoplasia
  Glioblastoma multiforme
  Rheumatoid arthritis
  Alzheimer disease
  Atopic dermatitis
  Breast neoplasm
  Carcinoma
  Clear cell renal carcinoma
  Colon cancer
  Colon carcinoma
  Colonic neoplasm
  Colorectal carcinoma
  Diabetic retinopathy
  Eosinophilic esophagitis
  Epithelial ovarian cancer
  Esophageal squamous cell carcinoma
  Gastric cancer
  Hashimoto thyroiditis
  Hepatocellular carcinoma
  Inflammatory bowel disease
  Irritable bowel syndrome
  Isolated neonatal sclerosing cholangitis
  Lung adenocarcinoma
  Neonatal ichthyosis-sclerosing cholangitis syndrome
  Pancreatic tumour
  Periodontitis
  Prostate cancer
  Prostate carcinoma
  Schizophrenia
  Squamous cell carcinoma
  Stomach cancer
  Stroke
  Thyroid gland papillary carcinoma
  B-cell neoplasm
  Contact dermatitis
  Lung cancer
  Lung carcinoma
  Non-small-cell lung cancer
  Non-syndromic ichthyosis
  Pancreatic cancer
  Triple negative breast cancer
  Endometriosis
  Colitis
  Colorectal neoplasm
  Metastatic malignant neoplasm
  Nasopharyngeal carcinoma
  Ovarian cancer
  Ovarian neoplasm
  Ulcerative colitis
• UniProt ID: CLD1_HUMAN
• Pfam ID: PF00822
• Sequence:
  MANAGLQLLGFILAFLGWIGAIVSTALPQWRIYSYAGDNIVTAQAMYEGLWMSCVSQSTG
  QIQCKVFDSLLNLSSTLQATRALMVVGILLGVIAIFVATVGMKCMKCLEDDEVQKMRMAV
  IGGAIFLLAGLAILVATAWYGNRIVQEFYDPMTPVNARYEFGQALFTGWAAASLCLLGGA
  LLCCSCPRKTTSYPTPRPYPKPAPSSGKDYV
• Function: Claudins function as major constituents of the tight junction complexes that regulate the permeability of epithelia. While some claudin family members play essential roles in the formation of impermeable barriers, others mediate the permeability to ions and small molecules. Often, several claudin family members are coexpressed and interact with each other, and this determines the overall permeability. CLDN1 is required to prevent the paracellular diffusion of small molecules through tight junctions in the epidermis and is required for the normal barrier function of the skin. Required for normal water homeostasis and to prevent excessive water loss through the skin, probably via an indirect effect on the expression levels of other proteins, since CLDN1 itself seems to be dispensable for water barrier formation in keratinocyte tight junctions ; (Microbial infection) Acts as a co-receptor for hepatitis C virus (HCV) in hepatocytes. Associates with CD81 and the CLDN1-CD81 receptor complex is essential for HCV entry into host cell. Acts as a receptor for dengue virus.
• Tissue Specificity: Strongly expressed in liver and kidney. Expressed in heart, brain, spleen, lung and testis.
• 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

49 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Anal intraepithelial neoplasia	DISJ0JW3	Definitive	Biomarker	[1]
Glioblastoma multiforme	DISK8246	Definitive	Biomarker	[2]
Rheumatoid arthritis	DISTSB4J	Definitive	Altered Expression	[3]
Alzheimer disease	DISF8S70	Strong	Biomarker	[4]
Atopic dermatitis	DISTCP41	Strong	Biomarker	[5]
Breast neoplasm	DISNGJLM	Strong	Genetic Variation	[6]
Carcinoma	DISH9F1N	Strong	Biomarker	[7]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[8]
Colon cancer	DISVC52G	Strong	Biomarker	[9]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[10]
Colonic neoplasm	DISSZ04P	Strong	Biomarker	[11]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[12]
Diabetic retinopathy	DISHGUJM	Strong	Altered Expression	[13]
Eosinophilic esophagitis	DISR8WSB	Strong	Altered Expression	[14]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[15]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[16]
Gastric cancer	DISXGOUK	Strong	Biomarker	[17]
Hashimoto thyroiditis	DIS77CDF	Strong	Altered Expression	[18]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[19]
Inflammatory bowel disease	DISGN23E	Strong	Altered Expression	[20]
Irritable bowel syndrome	DIS27206	Strong	Altered Expression	[20]
Isolated neonatal sclerosing cholangitis	DIS6G5UY	Strong	Genetic Variation	[21]
Lung adenocarcinoma	DISD51WR	Strong	Genetic Variation	[22]
Neonatal ichthyosis-sclerosing cholangitis syndrome	DISFCNXC	Strong	Autosomal recessive	[23]
Pancreatic tumour	DIS3U0LK	Strong	Altered Expression	[24]
Periodontitis	DISI9JOI	Strong	Biomarker	[25]
Prostate cancer	DISF190Y	Strong	Altered Expression	[26]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[26]
Schizophrenia	DISSRV2N	Strong	Biomarker	[27]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[16]
Stomach cancer	DISKIJSX	Strong	Biomarker	[17]
Stroke	DISX6UHX	Strong	Biomarker	[28]
Thyroid gland papillary carcinoma	DIS48YMM	Strong	Biomarker	[29]
B-cell neoplasm	DISVY326	moderate	Altered Expression	[30]
Contact dermatitis	DISQ3AU0	moderate	Genetic Variation	[31]
Lung cancer	DISCM4YA	moderate	Altered Expression	[32]
Lung carcinoma	DISTR26C	moderate	Altered Expression	[32]
Non-small-cell lung cancer	DIS5Y6R9	moderate	Altered Expression	[33]
Non-syndromic ichthyosis	DISZ9QBQ	moderate	Genetic Variation	[34]
Pancreatic cancer	DISJC981	moderate	Altered Expression	[35]
Triple negative breast cancer	DISAMG6N	moderate	Biomarker	[36]
Endometriosis	DISX1AG8	Disputed	Biomarker	[37]
Colitis	DISAF7DD	Limited	Biomarker	[20]
Colorectal neoplasm	DISR1UCN	Limited	Biomarker	[10]
Metastatic malignant neoplasm	DIS86UK6	Limited	Biomarker	[38]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Biomarker	[39]
Ovarian cancer	DISZJHAP	Limited	Altered Expression	[15]
Ovarian neoplasm	DISEAFTY	Limited	Altered Expression	[15]
Ulcerative colitis	DIS8K27O	Limited	Biomarker	[40]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Claudin-1 (CLDN1).	[41]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Claudin-1 (CLDN1).	[42]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Claudin-1 (CLDN1).	[43]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Claudin-1 (CLDN1).	[44]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Claudin-1 (CLDN1).	[45]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Claudin-1 (CLDN1).	[46]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Claudin-1 (CLDN1).	[47]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Claudin-1 (CLDN1).	[48]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Claudin-1 (CLDN1).	[49]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Claudin-1 (CLDN1).	[50]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Claudin-1 (CLDN1).	[51]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Claudin-1 (CLDN1).	[52]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Claudin-1 (CLDN1).	[41]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Claudin-1 (CLDN1).	[53]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Claudin-1 (CLDN1).	[54]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Claudin-1 (CLDN1).	[55]
Lucanthone	DMZLBUO	Approved	Lucanthone decreases the expression of Claudin-1 (CLDN1).	[56]
Acocantherin	DM7JT24	Approved	Acocantherin decreases the expression of Claudin-1 (CLDN1).	[57]
Sodium phenylbutyrate	DMXLBCQ	Approved	Sodium phenylbutyrate decreases the expression of Claudin-1 (CLDN1).	[58]
Hydroxychloroquine	DMSIVND	Approved	Hydroxychloroquine increases the expression of Claudin-1 (CLDN1).	[59]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Claudin-1 (CLDN1).	[41]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Claudin-1 (CLDN1).	[46]
Chloroquine	DMSI5CB	Phase 3 Trial	Chloroquine increases the expression of Claudin-1 (CLDN1).	[59]
CS-600G	DM1PV4Y	Phase 3	CS-600G increases the expression of Claudin-1 (CLDN1).	[60]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Claudin-1 (CLDN1).	[61]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Claudin-1 (CLDN1).	[63]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Claudin-1 (CLDN1).	[64]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Claudin-1 (CLDN1).	[65]
SB 203580	DMAET6F	Terminated	SB 203580 increases the expression of Claudin-1 (CLDN1).	[60]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Claudin-1 (CLDN1).	[67]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Claudin-1 (CLDN1).	[68]
chloropicrin	DMSGBQA	Investigative	chloropicrin affects the expression of Claudin-1 (CLDN1).	[69]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Claudin-1 (CLDN1).	[70]
Paraquat	DMR8O3X	Investigative	Paraquat decreases the expression of Claudin-1 (CLDN1).	[71]
Resorcinol	DMM37C0	Investigative	Resorcinol decreases the expression of Claudin-1 (CLDN1).	[72]
OXYRESVERATROL	DMN7S4L	Investigative	OXYRESVERATROL increases the expression of Claudin-1 (CLDN1).	[74]

4 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Phenol	DM1QSM3	Phase 2/3	Phenol affects the localization of Claudin-1 (CLDN1).	[62]
PMID26560530-Compound-35	DMO36RL	Patented	PMID26560530-Compound-35 affects the localization of Claudin-1 (CLDN1).	[66]
PATULIN	DM0RV9C	Investigative	PATULIN affects the localization of Claudin-1 (CLDN1).	[73]
Decanoic Acid	DM8FMYL	Investigative	Decanoic Acid affects the localization of Claudin-1 (CLDN1).	[75]

References

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