Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7G1WJW)

• DOT Name: Junctional cadherin 5-associated protein (JCAD)
• Synonyms: Junctional protein associated with coronary artery disease; JCAD
• Gene Name: JCAD
• Related Disease:
  Arteriosclerosis
  Atherosclerosis
  Cardiovascular disease
  Coronary atherosclerosis
  Myocardial infarction
  Advanced cancer
  Carcinoma of liver and intrahepatic biliary tract
  Coronary heart disease
  Liver cancer
  Neoplasm
  Non-alcoholic steatohepatitis
• UniProt ID: JCAD_HUMAN
• Pfam ID: PF15351
• Sequence:
  MYSVEDLLISHGYKLSRDPPASREDNPKGRQAARTGTRAGQGLQNGHEDGPAALAHRKTS
  AGKGHVSDSESRRSTPRGHGEPQSTSASRTSEAGFCNQPPSAWSSHPPTGNDQAYRRRGR
  QEARSQKPREHENLEARGMAQAHSLPVHVREGPWEVGGRSEHVMKKPVWEEELRMSGPAK
  WQNVSLESWNQPRKLGRQMSDGDGERLFQDLYPFIQGEHVLNSQNKGKSRSLPRVLSPES
  LSCTEIPIPLNERHSPKMPPYPPTCAPNLDSTRNSEKSGCSAPFPRPKFGRPLKPPSYSS
  HQQSRGGADSSDSQDSQQMDAYVPRHELCLSDPGLEPPVYVPPPSYRSPPQNIPNPYLED
  TVPINVCGGHSQQQSPTEKAGASGQPPSGPPGTGNEYGVSPRLPQGLPAHPRPVTAYDGF
  VQYIPFDDPRLRHFKLAQPQGFCEDIKLDDKSYNSSPVTAQEPAHGGMQPDGAIWNPQSL
  IPPSGDERGLVLADSSPRWLWGQPPGDGENSGLPNQRDRCVARGQWPDVRGSQHGHTGRQ
  VSSPYSQGESTCETQTKLKKFQTGTRTKKSSKKKMNETIFCLVSIPVKSESHLPDRDMDN
  NDLKPSADQKNGSDKSPALQEQSLLSMSSTDLELQALTGSMGGRTEFQKQDLGEPEEDRQ
  TNDLSFIHLTKHRELKHSGSWPGHRYRDQQTQTSFSEEPQSSQLLPGAKLGGPSRAALSP
  KCSDPAASEAQTHTAFPTGDHKQRPSARNLKGHRSLSPSSNSAFSRTSLSVDQAPTPKAG
  RSQPCVDVHGLGAHPGPKREVVKGEPTGPCNSKQLFGQFLLKPVSRRPWDLISQLESFNK
  ELQEEEESSSSSSSSSSSSEESEAEPQQENRAHCRQEDVGFRGNSPEMRVEPQPRMWVPE
  SPVCRSGRGESKSESWSEELQPGHPRAWPPSPGRFRVEEGGGAPFCSADGSTSAEKRHLE
  VSNGMDELAGSPFPVTRMSSRSSDAKPLPASYPAEPREPQESPKITSAFSSVKPSEAVPR
  KFDSGGERGAGLPLSLSNKNRGLSAPDLRSVGLTPGQEQGASELEGSLGEASTIEIPPGE
  SLQARAARILGIEVAVESLLPGIRRAGQNQPAEPDASACTPESPQEELLSRPAPADVPRV
  STDAFYGRRKCGWTKSPLFVGDRDSARRAPQAFEHSDVDGVVTSTDPVPEPEPSPLESKF
  FEQKDVETKPPFRSTLFHFVERTPSVAGSEKRLRSPSKVIESLQEKLASPPRRADPDRLM
  RMKEVSSVSRMRVLSFRNADSQEDAEELKATTRGQAGLPGGLVSPGSGDRAQRLGHSLSV
  SKDSISREEKEHPAAQKEKSMDQDFWCPDSYDPSRVERV

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[1]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[1]
Cardiovascular disease	DIS2IQDX	Strong	Biomarker	[2]
Coronary atherosclerosis	DISKNDYU	Strong	Genetic Variation	[1]
Myocardial infarction	DIS655KI	Strong	Biomarker	[3]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[4]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Limited	Biomarker	[4]
Coronary heart disease	DIS5OIP1	Limited	Genetic Variation	[1]
Liver cancer	DISDE4BI	Limited	Biomarker	[4]
Neoplasm	DISZKGEW	Limited	Biomarker	[4]
Non-alcoholic steatohepatitis	DIST4788	Limited	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Junctional cadherin 5-associated protein (JCAD).	[5]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Junctional cadherin 5-associated protein (JCAD).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Junctional cadherin 5-associated protein (JCAD).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Junctional cadherin 5-associated protein (JCAD).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Junctional cadherin 5-associated protein (JCAD).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Junctional cadherin 5-associated protein (JCAD).	[8]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Junctional cadherin 5-associated protein (JCAD).	[9]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Junctional cadherin 5-associated protein (JCAD).	[11]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Junctional cadherin 5-associated protein (JCAD).	[11]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Junctional cadherin 5-associated protein (JCAD).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Junctional cadherin 5-associated protein (JCAD).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Junctional cadherin 5-associated protein (JCAD).	[14]
Nitrobenzanthrone	DMN6L70	Investigative	Nitrobenzanthrone increases the expression of Junctional cadherin 5-associated protein (JCAD).	[15]

References

• [1] The novel coronary artery disease risk gene JCAD/KIAA1462 promotes endothelial dysfunction and atherosclerosis.Eur Heart J. 2019 Aug 1;40(29):2398-2408. doi: 10.1093/eurheartj/ehz303.
• [2] KIAA1462, a coronary artery disease associated gene, is a candidate gene for late onset Alzheimer disease in APOE carriers.PLoS One. 2013 Dec 12;8(12):e82194. doi: 10.1371/journal.pone.0082194. eCollection 2013.
• [3] The association of functional polymorphisms in genes expressed in endothelial cells and smooth muscle cells with the myocardial infarction.Hum Genomics. 2019 Jan 24;13(1):5. doi: 10.1186/s40246-018-0189-8.
• [4] JCAD Promotes Progression of Nonalcoholic Steatohepatitis to Liver Cancer by Inhibiting LATS2 Kinase Activity.Cancer Res. 2017 Oct 1;77(19):5287-5300. doi: 10.1158/0008-5472.CAN-17-0229. Epub 2017 Aug 3.
• [5] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [6] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [7] 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.
• [8] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [9] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [10] 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.
• [11] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [12] 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.
• [13] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [14] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [15] 3-Nitrobenzanthrone promotes malignant transformation in human lung epithelial cells through the epiregulin-signaling pathway. Cell Biol Toxicol. 2022 Oct;38(5):865-887. doi: 10.1007/s10565-021-09612-1. Epub 2021 May 25.