Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFZF1ST)

• DOT Name: Protocadherin beta-14 (PCDHB14)
• Synonyms: PCDH-beta-14
• Gene Name: PCDHB14
• UniProt ID: PCDBE_HUMAN
• Pfam ID: PF00028 ; PF08266 ; PF16492
• Sequence:
  MEIRGALDLRKRQVLIFLVLLGLSRAGTESAHYSVAEETEIGSFVANLARDLGLGVEELS
  SREARVVSDDNKKYLHLDLLTGNLLLNEKLDRDELCGSTEPCVLHFQVVLENPLQFFRFE
  LCVKDINDHSPTFLDKEILIKISEGTTVGATFLMESAQDLDVGSNSLQNYTISPNSHFYI
  KIPDSSDRKIYPELVLDRALDYEQEAELRLTLTAVDGGSPPKSGTTLVLIKVLDINDNAP
  EFPQSLYEVQVPEDRPLGSWIATISAKDLDAGNYGKISYTFFHASEDIRKTFEINPISGE
  VNLRSPLDFEVIQSYTINIQATDGGGLSGKCTLLVKVMDINDNPPEVTISSITKRIPENA
  SETLVALFSILDQDSGDNGRMICSIQDNLPFFLKPTFKNFFTLVSEKALDRESQAEYNIT
  ITVTDLGTPRLKTEYNITVLLSDVNDNAPTFTQTSYTLFVRENNSPALHIGSVSATDRDS
  GTNAQVNYSLLPPQDRHLPLASLVSINADNGHLFALRSLDYEALQEFEFRVGATDRGSPA
  LSSEALVRVLVLDANDNSPFVLYPLQNGSAPCTELVPRAAEPGYLVTKVVAVDGDSGQNA
  WLSYQLLKATEPGLFGVWAHNGEVRTARLLSERDAAKHRLVVLVKDNGEPPRSATATLHV
  LLVDGFSQPYLPLPEAAPAQAQADSLTVYLVVALASVSSLFLFSVLLFVAVRLCRRSRAA
  SVGRCSVPEGPFPGHLVDVSGTGTLSQSYQYEVCLTGGSGTNEFKFLKPIIPNFQVHDTG
  RNMGEIENFRNSFGLNIQ
• Function: Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain.

Molecular Interaction Atlas (MIA) of This DOT

13 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 Protocadherin beta-14 (PCDHB14).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protocadherin beta-14 (PCDHB14).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Protocadherin beta-14 (PCDHB14).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protocadherin beta-14 (PCDHB14).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Protocadherin beta-14 (PCDHB14).	[5]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Protocadherin beta-14 (PCDHB14).	[6]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Protocadherin beta-14 (PCDHB14).	[7]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Protocadherin beta-14 (PCDHB14).	[1]
Azacitidine	DMTA5OE	Approved	Azacitidine decreases the expression of Protocadherin beta-14 (PCDHB14).	[8]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Protocadherin beta-14 (PCDHB14).	[1]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Protocadherin beta-14 (PCDHB14).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Protocadherin beta-14 (PCDHB14).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Protocadherin beta-14 (PCDHB14).	[13]

2 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 increases the methylation of Protocadherin beta-14 (PCDHB14).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Protocadherin beta-14 (PCDHB14).	[11]

References

• [1] 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.
• [2] 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.
• [3] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [4] 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.
• [5] 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.
• [6] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [7] JunD is involved in the antiproliferative effect of Delta9-tetrahydrocannabinol on human breast cancer cells. Oncogene. 2008 Aug 28;27(37):5033-44.
• [8] The effect of DNA methylation inhibitor 5-Aza-2'-deoxycytidine on human endometrial stromal cells. Hum Reprod. 2010 Nov;25(11):2859-69.
• [9] 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.
• [10] 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.
• [11] Expression and DNA methylation changes in human breast epithelial cells after bisphenol A exposure. Int J Oncol. 2012 Jul;41(1):369-77.
• [12] 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.
• [13] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.