Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSXEQF7)

• DOT Name: PPP2R1A-PPP2R2A-interacting phosphatase regulator 1 (PABIR1)
• Synonyms: PABIR family member 1
• Gene Name: PABIR1
• UniProt ID: PBIR1_HUMAN
• PDB ID: 8SO0; 8TWE; 8TWI
• Sequence:
  MAQEKMELDLELPPGTGGSPAEGGGSGGGGGLRRSNSAPLIHGLSDTSPVFQAEAPSARR
  NSTTFPSRHGLLLPASPVRMHSSRLHQIKQEEGMDLINRETVHEREVQTAMQISHSWEES
  FSLSDNDVEKSASPKRIDFIPVSPAPSPTRGIGKQCFSPSLQSFVSSNGLPPSPIPSPTT
  RFTTRRSQSPINCIRPSVLGPLKRKCEMETEYQPKRFFQGITNMLSSDVAQLSDPGVCVS
  SDTLDGNSSSAGSSCNSPAKVSTTTDSPVSPAQAASPFIPLDELSSK
• Function: Acts as an inhibitor of serine/threonine-protein phosphatase 2A (PP2A) activity. Potentiates ubiquitin-mediated proteasomal degradation of serine/threonine-protein phosphatase 2A catalytic subunit alpha (PPP2CA). Inhibits PP2A-mediated dephosphorylation of WEE1, promoting ubiquitin-mediated proteolysis of WEE1, thereby releasing G2/M checkpoint.

Molecular Interaction Atlas (MIA) of This DOT

10 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 PPP2R1A-PPP2R2A-interacting phosphatase regulator 1 (PABIR1).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of PPP2R1A-PPP2R2A-interacting phosphatase regulator 1 (PABIR1).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of PPP2R1A-PPP2R2A-interacting phosphatase regulator 1 (PABIR1).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of PPP2R1A-PPP2R2A-interacting phosphatase regulator 1 (PABIR1).	[4]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of PPP2R1A-PPP2R2A-interacting phosphatase regulator 1 (PABIR1).	[6]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of PPP2R1A-PPP2R2A-interacting phosphatase regulator 1 (PABIR1).	[7]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of PPP2R1A-PPP2R2A-interacting phosphatase regulator 1 (PABIR1).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of PPP2R1A-PPP2R2A-interacting phosphatase regulator 1 (PABIR1).	[9]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of PPP2R1A-PPP2R2A-interacting phosphatase regulator 1 (PABIR1).	[10]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID increases the expression of PPP2R1A-PPP2R2A-interacting phosphatase regulator 1 (PABIR1).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Quercetin	DM3NC4M	Approved	Quercetin affects the phosphorylation of PPP2R1A-PPP2R2A-interacting phosphatase regulator 1 (PABIR1).	[5]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of PPP2R1A-PPP2R2A-interacting phosphatase regulator 1 (PABIR1).	[5]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of PPP2R1A-PPP2R2A-interacting phosphatase regulator 1 (PABIR1).	[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] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] The molecular basis of genistein-induced mitotic arrest and exit of self-renewal in embryonal carcinoma and primary cancer cell lines. BMC Med Genomics. 2008 Oct 10;1:49.
• [8] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [9] 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.
• [10] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [11] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.