Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKY7W52)

• DOT Name: PRKC apoptosis WT1 regulator protein (PAWR)
• Synonyms: Prostate apoptosis response 4 protein; Par-4
• Gene Name: PAWR
• UniProt ID: PAWR_HUMAN
• PDB ID: 2JK9
• Sequence:
  MATGGYRTSSGLGGSTTDFLEEWKAKREKMRAKQNPPGPAPPGGGSSDAAGKPPAGALGT
  PAAAAANELNNNLPGGAPAAPAVPGPGGVNCAVGSAMLTRAAPGPRRSEDEPPAASASAA
  PPPQRDEEEPDGVPEKGKSSGPSARKGKGQIEKRKLREKRRSTGVVNIPAAECLDEYEDD
  EAGQKERKREDAITQQNTIQNEAVNLLDPGSSYLLQEPPRTVSGRYKSTTSVSEEDVSSR
  YSRTDRSGFPRYNRDANVSGTLVSSSTLEKKIEDLEKEVVRERQENLRLVRLMQDKEEMI
  GKLKEEIDLLNRDLDDIEDENEQLKQENKTLLKVVGQLTR
• Function: Pro-apoptotic protein capable of selectively inducing apoptosis in cancer cells, sensitizing the cells to diverse apoptotic stimuli and causing regression of tumors in animal models. Induces apoptosis in certain cancer cells by activation of the Fas prodeath pathway and coparallel inhibition of NF-kappa-B transcriptional activity. Inhibits the transcriptional activation and augments the transcriptional repression mediated by WT1. Down-regulates the anti-apoptotic protein BCL2 via its interaction with WT1. Seems also to be a transcriptional repressor by itself. May be directly involved in regulating the amyloid precursor protein (APP) cleavage activity of BACE1.
• Tissue Specificity: Widely expressed. Expression is elevated in various neurodegenerative diseases such as amyotrophic lateral sclerosis, Alzheimer, Parkinson and Huntington diseases and stroke. Down-regulated in several cancers.

Molecular Interaction Atlas (MIA) of This DOT

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 PRKC apoptosis WT1 regulator protein (PAWR).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of PRKC apoptosis WT1 regulator protein (PAWR).	[20]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of PRKC apoptosis WT1 regulator protein (PAWR).	[23]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of PRKC apoptosis WT1 regulator protein (PAWR).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of PRKC apoptosis WT1 regulator protein (PAWR).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of PRKC apoptosis WT1 regulator protein (PAWR).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of PRKC apoptosis WT1 regulator protein (PAWR).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of PRKC apoptosis WT1 regulator protein (PAWR).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of PRKC apoptosis WT1 regulator protein (PAWR).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of PRKC apoptosis WT1 regulator protein (PAWR).	[9]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of PRKC apoptosis WT1 regulator protein (PAWR).	[10]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of PRKC apoptosis WT1 regulator protein (PAWR).	[11]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of PRKC apoptosis WT1 regulator protein (PAWR).	[12]
Menadione	DMSJDTY	Approved	Menadione affects the expression of PRKC apoptosis WT1 regulator protein (PAWR).	[11]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of PRKC apoptosis WT1 regulator protein (PAWR).	[13]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of PRKC apoptosis WT1 regulator protein (PAWR).	[14]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of PRKC apoptosis WT1 regulator protein (PAWR).	[15]
Menthol	DMG2KW7	Approved	Menthol increases the expression of PRKC apoptosis WT1 regulator protein (PAWR).	[16]
Sodium phenylbutyrate	DMXLBCQ	Approved	Sodium phenylbutyrate decreases the expression of PRKC apoptosis WT1 regulator protein (PAWR).	[17]
Bendamustine hydrochloride	DMFH15Z	Approved	Bendamustine hydrochloride decreases the expression of PRKC apoptosis WT1 regulator protein (PAWR).	[18]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of PRKC apoptosis WT1 regulator protein (PAWR).	[19]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of PRKC apoptosis WT1 regulator protein (PAWR).	[21]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of PRKC apoptosis WT1 regulator protein (PAWR).	[22]
Nimesulide	DMR1NMD	Terminated	Nimesulide increases the expression of PRKC apoptosis WT1 regulator protein (PAWR).	[24]
NS398	DMINUWH	Terminated	NS398 increases the expression of PRKC apoptosis WT1 regulator protein (PAWR).	[24]
SC-58125	DM874YU	Terminated	SC-58125 increases the expression of PRKC apoptosis WT1 regulator protein (PAWR).	[24]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of PRKC apoptosis WT1 regulator protein (PAWR).	[25]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of PRKC apoptosis WT1 regulator protein (PAWR).	[26]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of PRKC apoptosis WT1 regulator protein (PAWR).	[27]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin affects the localization of PRKC apoptosis WT1 regulator protein (PAWR).	[3]

References

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