Details of Drug Off-Target (DOT)

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

• DOT Name: Claudin domain-containing protein 1 (CLDND1)
• Synonyms: Membrane protein GENX-3745
• Gene Name: CLDND1
• Related Disease:
  Breast cancer
  Breast carcinoma
  Cardiovascular disease
  Cerebral infarction
  Cerebrovascular disease
  Type-1/2 diabetes
• UniProt ID: CLDN1_HUMAN
• Pfam ID: PF13903
• Sequence:
  MDNRFATAFVIACVLSLISTIYMAASIGTDFWYEYRSPVQENSSDLNKSIWDEFISDEAD
  EKTYNDALFRYNGTVGLWRRCITIPKNMHWYSPPERTESFDVVTKCVSFTLTEQFMEKFV
  DPGNHNSGIDLLRTYLWRCQFLLPFVSLGLMCFGALIGLCACICRSLYPTIATGILHLLA
  GLCTLGSVSCYVAGIELLHQKLELPDNVSGEFGWSFCLACVSAPLQFMASALFIWAAHTN
  RKEYTLMKAYRVA
• Tissue Specificity: Widely distributed in the adult CNS with highest expression in the corpus callosum, caudate nucleus, cerebral cortex, medulla, putamen, spinal cord, substantia nigra and subthalamic nucleus. Weak expression was detected in the adult heart.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Definitive	Biomarker	[1]
Breast carcinoma	DIS2UE88	Definitive	Biomarker	[1]
Cardiovascular disease	DIS2IQDX	Strong	Altered Expression	[2]
Cerebral infarction	DISR1WNP	Strong	Altered Expression	[3]
Cerebrovascular disease	DISAB237	Strong	Altered Expression	[3]
Type-1/2 diabetes	DISIUHAP	Strong	Altered Expression	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Claudin domain-containing protein 1 (CLDND1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Claudin domain-containing protein 1 (CLDND1).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Claudin domain-containing protein 1 (CLDND1).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Claudin domain-containing protein 1 (CLDND1).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Claudin domain-containing protein 1 (CLDND1).	[8]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Claudin domain-containing protein 1 (CLDND1).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Claudin domain-containing protein 1 (CLDND1).	[10]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Claudin domain-containing protein 1 (CLDND1).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Claudin domain-containing protein 1 (CLDND1).	[12]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Claudin domain-containing protein 1 (CLDND1).	[13]

References

• [1] Down Regulation of CLDND1 Induces Apoptosis in Breast Cancer Cells.PLoS One. 2015 Jun 17;10(6):e0130300. doi: 10.1371/journal.pone.0130300. eCollection 2015.
• [2] The retinoic acid receptor-related orphan receptor positively regulates tight junction protein claudin domain-containing 1 mRNA expression in human brain endothelial cells.J Biochem. 2017 May 1;161(5):441-450. doi: 10.1093/jb/mvw092.
• [3] Levels of tight junction protein CLDND1 are regulated by microRNA-124 in the cerebellum of stroke-prone spontaneously hypertensive rats.Biochem Biophys Res Commun. 2018 Apr 15;498(4):817-823. doi: 10.1016/j.bbrc.2018.03.063. Epub 2018 Mar 13.
• [4] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [5] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [8] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [11] Highly active combination of BRD4 antagonist and histone deacetylase inhibitor against human acute myelogenous leukemia cells. Mol Cancer Ther. 2014 May;13(5):1142-54.
• [12] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [13] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.