Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCT7YPX)

• DOT Name: Protein prenyltransferase alpha subunit repeat-containing protein 1 (PTAR1)
• Gene Name: PTAR1
• UniProt ID: PTAR1_HUMAN
• PDB ID: 6J6X; 6J74; 6J7F; 6J7X; 6O60
• Pfam ID: PF01239
• Sequence:
  MAETSEEVAVLVQRVVKDITNAFRRNPHIDEIGLIPCPEARYNRSPIVLVENKLGVESWC
  VKFLLPYVHNKLLLYRTRKQWLNRDELIDVTCTLLLLNPDFTTAWNVRKELILSGTLNPI
  KDLHLGKLALTKFPKSPETWIHRRWVLQQLIQETSLPSFVTKGNLGTIPTERAQRLIQEE
  MEVCGEAAGRYPSNYNAWSHRIWVLQHLAKLDVKILLDELSSTKHWASMHVSDHSGFHYR
  QFLLKSLISQTVIDSSVMEQNPLRSEPALVPPKDEEAAVSTEEPRINLPHLLEEEVEFST
  DLIDSYPGHETLWCHRRHIFYLQHHLNAGSQLSQAMEVDGLNDSSKQGYSQETKRLKRTP
  VPDSLGLEMEHRFIDQVLSTCRNVEQARFASAYRKWLVTLSQ

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Camptothecin	DM6CHNJ	Phase 3	Protein prenyltransferase alpha subunit repeat-containing protein 1 (PTAR1) decreases the response to substance of Camptothecin.	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Protein prenyltransferase alpha subunit repeat-containing protein 1 (PTAR1).	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Protein prenyltransferase alpha subunit repeat-containing protein 1 (PTAR1).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Protein prenyltransferase alpha subunit repeat-containing protein 1 (PTAR1).	[3]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Protein prenyltransferase alpha subunit repeat-containing protein 1 (PTAR1).	[4]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Protein prenyltransferase alpha subunit repeat-containing protein 1 (PTAR1).	[5]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Protein prenyltransferase alpha subunit repeat-containing protein 1 (PTAR1).	[6]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Protein prenyltransferase alpha subunit repeat-containing protein 1 (PTAR1).	[7]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Protein prenyltransferase alpha subunit repeat-containing protein 1 (PTAR1).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Protein prenyltransferase alpha subunit repeat-containing protein 1 (PTAR1).	[9]

References

• [1] 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.
• [2] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [3] 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.
• [4] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [5] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [6] 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.
• [7] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [8] Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach. BMC Syst Biol. 2012 Dec 10;6:152.
• [9] 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.
• [10] ATR inhibitors VE-821 and VX-970 sensitize cancer cells to topoisomerase i inhibitors by disabling DNA replication initiation and fork elongation responses. Cancer Res. 2014 Dec 1;74(23):6968-79.