Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7PF813)

• DOT Name: Chondroadherin (CHAD)
• Synonyms: Cartilage leucine-rich protein
• Gene Name: CHAD
• Related Disease:
  Osteoporosis
  Prostate cancer
  Prostate carcinoma
  Hepatocellular carcinoma
  Neoplasm
  Squamous cell carcinoma
• UniProt ID: CHAD_HUMAN
• PDB ID: 5LFN; 5MX1
• Pfam ID: PF13855 ; PF01462
• Sequence:
  MVRPMLLLSLGLLAGLLPALAACPQNCHCHSDLQHVICDKVGLQKIPKVSEKTKLLNLQR
  NNFPVLAANSFRAMPNLVSLHLQHCQIREVAAGAFRGLKQLIYLYLSHNDIRVLRAGAFD
  DLTELTYLYLDHNKVTELPRGLLSPLVNLFILQLNNNKIRELRAGAFQGAKDLRWLYLSE
  NALSSLQPGALDDVENLAKFHVDRNQLSSYPSAALSKLRVVEELKLSHNPLKSIPDNAFQ
  SFGRYLETLWLDNTNLEKFSDGAFLGVTTLKHVHLENNRLNQLPSNFPFDSLETLALTNN
  PWKCTCQLRGLRRWLEAKASRPDATCASPAKFKGQHIRDTDAFRSCKFPTKRSKKAGRH
• Function: Promotes attachment of chondrocytes, fibroblasts, and osteoblasts. This binding is mediated (at least for chondrocytes and fibroblasts) by the integrin alpha(2)beta(1). May play an important role in the regulation of chondrocyte growth and proliferation.
• Tissue Specificity: Present in chondrocytes at all ages.
• KEGG Pathway:
  PI3K-Akt sig.ling pathway (hsa04151)
  Focal adhesion (hsa04510)
  ECM-receptor interaction (hsa04512)
  Human papillomavirus infection (hsa05165)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Osteoporosis	DISF2JE0	Strong	Biomarker	[1]
Prostate cancer	DISF190Y	Strong	Biomarker	[2]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[2]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[3]
Neoplasm	DISZKGEW	moderate	Altered Expression	[3]
Squamous cell carcinoma	DISQVIFL	moderate	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Chondroadherin (CHAD).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Chondroadherin (CHAD).	[6]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Chondroadherin (CHAD).	[8]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Chondroadherin (CHAD).	[7]

References

• [1] The C-terminal domain of chondroadherin: a new regulator of osteoclast motility counteracting bone loss.J Bone Miner Res. 2014 Aug;29(8):1833-46. doi: 10.1002/jbmr.2206.
• [2] Whole exome sequencing in 75 high-risk families with validation and replication in independent case-control studies identifies TANGO2, OR5H14, and CHAD as new prostate cancer susceptibility genes.Oncotarget. 2017 Jan 3;8(1):1495-1507. doi: 10.18632/oncotarget.13646.
• [3] Tumor repressor gene chondroadherin oppose migration and proliferation in hepatocellular carcinoma and predicts a good survival.Oncotarget. 2017 Aug 2;8(36):60270-60279. doi: 10.18632/oncotarget.19811. eCollection 2017 Sep 1.
• [4] DNA methylation biomarkers for lung cancer.Tumour Biol. 2012 Apr;33(2):287-96. doi: 10.1007/s13277-011-0282-2. Epub 2011 Dec 6.
• [5] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [6] Pretreatment of 3-MA prevents doxorubicin-induced cardiotoxicity through inhibition of autophagy initiation. Toxicology. 2023 May 15;490:153512. doi: 10.1016/j.tox.2023.153512. Epub 2023 Apr 14.
• [7] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [8] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.