Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2X0IFQ)

• DOT Name: Plexin domain-containing protein 1 (PLXDC1)
• Synonyms: Tumor endothelial marker 3; Tumor endothelial marker 7
• Gene Name: PLXDC1
• UniProt ID: PLDX1_HUMAN
• Pfam ID: PF01437
• Sequence:
  MRGELWLLVLVLREAARALSPQPGAGHDEGPGSGWAAKGTVRGWNRRARESPGHVSEPDR
  TQLSQDLGGGTLAMDTLPDNRTRVVEDNHSYYVSRLYGPSEPHSRELWVDVAEANRSQVK
  IHTILSNTHRQASRVVLSFDFPFYGHPLRQITIATGGFIFMGDVIHRMLTATQYVAPLMA
  NFNPGYSDNSTVVYFDNGTVFVVQWDHVYLQGWEDKGSFTFQAALHHDGRIVFAYKEIPM
  SVPEISSSQHPVKTGLSDAFMILNPSPDVPESRRRSIFEYHRIELDPSKVTSMSAVEFTP
  LPTCLQHRSCDACMSSDLTFNCSWCHVLQRCSSGFDRYRQEWMDYGCAQEAEGRMCEDFQ
  DEDHDSASPDTSFSPYDGDLTTTSSSLFIDSLTTEDDTKLNPYAGGDGLQNNLSPKTKGT
  PVHLGTIVGIVLAVLLVAAIILAGIYINGHPTSNAALFFIERRPHHWPAMKFRSHPDHST
  YAEVEPSGHEKEGFMEAEQC
• Function: Plays a critical role in endothelial cell capillary morphogenesis.
• Tissue Specificity: Detected in urine (at protein level) . Detected in endothelial cells from colorectal cancer, and in endothelial cells from primary cancers of the lung, liver, pancreas, breast and brain. Not detectable in endothelial cells from normal tissue. Expressed in fibrovascular membrane with increased expression in individuals with proliferative diabetic retinopathy.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Plexin domain-containing protein 1 (PLXDC1).	[1]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Plexin domain-containing protein 1 (PLXDC1).	[2]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Plexin domain-containing protein 1 (PLXDC1).	[3]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Plexin domain-containing protein 1 (PLXDC1).	[2]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Plexin domain-containing protein 1 (PLXDC1).	[4]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Plexin domain-containing protein 1 (PLXDC1).	[6]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Plexin domain-containing protein 1 (PLXDC1).	[7]

1 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 decreases the methylation of Plexin domain-containing protein 1 (PLXDC1).	[5]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] 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.
• [3] Effects of progesterone treatment on expression of genes involved in uterine quiescence. Reprod Sci. 2011 Aug;18(8):781-97.
• [4] Anti-proliferative and gene expression actions of resveratrol in breast cancer cells in vitro. Oncotarget. 2014 Dec 30;5(24):12891-907.
• [5] 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.
• [6] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
• [7] 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.