Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCJD85N)

• DOT Name: Papilin (PAPLN)
• Gene Name: PAPLN
• Related Disease:
  Neoplasm
  Capillary hemangioma
  Hemangioma
  Lung cancer
  Lung carcinoma
  Varicose veins
• UniProt ID: PPN_HUMAN
• Pfam ID: PF19236 ; PF05986 ; PF07679 ; PF00014 ; PF16626 ; PF08686 ; PF19030 ; PF00090
• Sequence:
  MRLLLLVPLLLAPAPGSSAPKVRRQSDTWGPWSQWSPCSRTCGGGVSFRERPCYSQRRDG
  GSSCVGPARSHRSCRTESCPDGARDFRAEQCAEFDGAEFQGRRYRWLPYYSAPNKCELNC
  IPKGENFYYKHREAVVDGTPCEPGKRDVCVDGSCRVVGCDHELDSSKQEDKCLRCGGDGT
  TCYPVAGTFDANDLSRGYNQILIVPMGATSILIDEAAASRNFLAVKNVRGEYYLNGHWTI
  EAARALPAASTILHYERGAEGDLAPERLHARGPTSEPLVIELISQEPNPGVHYEYHLPLR
  RPSPGFSWSHGSWSDCSAECGGGHQSRLVFCTIDHEAYPDHMCQRQPRPADRRSCNLHPC
  PETKRWKAGPWAPCSASCGGGSQSRSVYCISSDGAGIQEAVEEAECAGLPGKPPAIQACN
  LQRCAAWSPEPWGECSVSCGVGVRKRSVTCRGERGSLLHTAACSLEDRPPLTEPCVHEDC
  PLLSDQAWHVGTWGLCSKSCSSGTRRRQVICAIGPPSHCGSLQHSKPVDVEPCNTQPCHL
  PQEVPSMQDVHTPASNPWMPLGPQESPASDSRGQWWAAQEHPSARGDHRGERGDPRGDQG
  THLSALGPAPSLQQPPYQQPLRSGSGPHDCRHSPHGCCPDGHTASLGPQWQGCPGAPCQQ
  SRYGCCPDRVSVAEGPHHAGCTKSYGGDSTGGMPRSRAVASTVHNTHQPQAQQNEPSECR
  GSQFGCCYDNVATAAGPLGEGCVGQPSHAYPVRCLLPSAHGSCADWAARWYFVASVGQCN
  RFWYGGCHGNANNFASEQECMSSCQGSLHGPRRPQPGASGRSTHTDGGGSSPAGEQEPSQ
  HRTGAAVQRKPWPSGGLWRQDQQPGPGEAPHTQAFGEWPWGQELGSRAPGLGGDAGSPAP
  PFHSSSYRISLAGVEPSLVQAALGQLVRLSCSDDTAPESQAAWQKDGQPISSDRHRLQFD
  GSLIIHPLQAEDAGTYSCGSTRPGRDSQKIQLRIIGGDMAVLSEAELSRFPQPRDPAQDF
  GQAGAAGPLGAIPSSHPQPANRLRLDQNQPRVVDASPGQRIRMTCRAEGFPPPAIEWQRD
  GQPVSSPRHQLQPDGSLVISRVAVEDGGFYTCVAFNGQDRDQRWVQLRVLGELTISGLPP
  TVTVPEGDTARLLCVVAGESVNIRWSRNGLPVQADGHRVHQSPDGTLLIYNLRARDEGSY
  TCSAYQGSQAVSRSTEVKVVSPAPTAQPRDPGRDCVDQPELANCDLILQAQLCGNEYYSS
  FCCASCSRFQPHAQPIWQ

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Biomarker	[1]
Capillary hemangioma	DISQ8XPT	Strong	Biomarker	[2]
Hemangioma	DISDCGAG	Strong	Biomarker	[2]
Lung cancer	DISCM4YA	Strong	Biomarker	[3]
Lung carcinoma	DISTR26C	Strong	Biomarker	[3]
Varicose veins	DISIMBN2	Strong	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 Papilin (PAPLN).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Papilin (PAPLN).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Papilin (PAPLN).	[10]

6 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 Papilin (PAPLN).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Papilin (PAPLN).	[7]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Papilin (PAPLN).	[7]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Papilin (PAPLN).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Papilin (PAPLN).	[11]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Papilin (PAPLN).	[12]

References

• [1] Novel hyaluronic acid-modified temperature-sensitive nanoparticles for synergistic chemo-photothermal therapy.Carbohydr Polym. 2019 Jun 15;214:221-233. doi: 10.1016/j.carbpol.2019.03.043. Epub 2019 Mar 14.
• [2] PLGA nanoparticles with CD133 aptamers for targeted delivery and sustained release of propranolol to hemangioma.Nanomedicine (Lond). 2017 Nov;12(21):2611-2624. doi: 10.2217/nnm-2017-0130. Epub 2017 Sep 29.
• [3] Suppression of PPN/MG61 attenuates Wnt/beta-catenin signaling pathway and induces apoptosis in human lung cancer.Oncogene. 2008 May 29;27(24):3483-8. doi: 10.1038/sj.onc.1211006. Epub 2008 Jan 14.
• [4] The pedunculopontine and laterodorsal tegmental nuclei in the kainate model of epilepsy.Neurosci Lett. 2018 Apr 13;672:90-95. doi: 10.1016/j.neulet.2018.02.044. Epub 2018 Feb 21.
• [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] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [8] 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.
• [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] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [11] 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.
• [12] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.