Details of Drug Off-Target (DOT)

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

• DOT Name: Transcriptional regulator protein Pur-beta (PURB)
• Synonyms: Purine-rich element-binding protein B
• Gene Name: PURB
• Related Disease:
  Acute myelogenous leukaemia
  Cardiac failure
  Childhood myelodysplastic syndrome
  Congestive heart failure
  Myelodysplastic syndrome
• UniProt ID: PURB_HUMAN
• Pfam ID: PF04845
• Sequence:
  MADGDSGSERGGGGGPCGFQPASRGGGEQETQELASKRLDIQNKRFYLDVKQNAKGRFLK
  IAEVGAGGSKSRLTLSMAVAAEFRDSLGDFIEHYAQLGPSSPEQLAAGAEEGGGPRRALK
  SEFLVRENRKYYLDLKENQRGRFLRIRQTVNRGGGGFGAGPGPGGLQSGQTIALPAQGLI
  EFRDALAKLIDDYGGEDDELAGGPGGGAGGPGGGLYGELPEGTSITVDSKRFFFDVGCNK
  YGVFLRVSEVKPSYRNAITVPFKAWGKFGGAFCRYADEMKEIQERQRDKLYERRGGGSGG
  GEESEGEEVDED
• Function: Transcriptional regulator which can act as an activator or a repressor. Represses the transcription of ACTA2 in fibroblasts and smooth muscle cells via its ability to interact with the purine-rich strand of a MCAT- containing element in the 5' flanking region of the gene. Represses the transcription of MYOCD, capable of repressing all isoforms of MYOCD but the magnitude of the repressive effects is most notable for the SMC- specific isoforms. Promotes hepatic glucose production by activating the transcription of ADCY6, leading to cAMP accumulation, increased PKA activity, CREB activation, and increased transcription of PCK1 and G6PC genes. Has capacity to bind repeated elements in single-stranded DNA such as the purine-rich single strand of the PUR element located upstream of the MYC gene. Participates in transcriptional and translational regulation of alpha-MHC expression in cardiac myocytes by binding to the purine-rich negative regulatory (PNR) element Modulates constitutive liver galectin-3 gene transcription by binding to its promoter. May play a role in the dendritic transport of a subset of mRNAs.
• Tissue Specificity: Expressed in myocardium of heart failure patients.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Definitive	Biomarker	[1]
Cardiac failure	DISDC067	Strong	Altered Expression	[2]
Childhood myelodysplastic syndrome	DISMN80I	Strong	Biomarker	[3]
Congestive heart failure	DIS32MEA	Strong	Altered Expression	[2]
Myelodysplastic syndrome	DISYHNUI	Strong	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Transcriptional regulator protein Pur-beta (PURB).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Transcriptional regulator protein Pur-beta (PURB).	[5]
Haloperidol	DM96SE0	Approved	Haloperidol decreases the expression of Transcriptional regulator protein Pur-beta (PURB).	[6]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Transcriptional regulator protein Pur-beta (PURB).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Transcriptional regulator protein Pur-beta (PURB).	[8]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Transcriptional regulator protein Pur-beta (PURB).	[9]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Transcriptional regulator protein Pur-beta (PURB).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Transcriptional regulator protein Pur-beta (PURB).	[12]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Transcriptional regulator protein Pur-beta (PURB).	[13]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of Transcriptional regulator protein Pur-beta (PURB).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Transcriptional regulator protein Pur-beta (PURB).	[10]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Transcriptional regulator protein Pur-beta (PURB).	[10]

References

• [1] Characterization of purine-rich element binding protein B as a novel biomarker in acute myelogenous leukemia prognostication.J Cell Biochem. 2018 Feb;119(2):2073-2083. doi: 10.1002/jcb.26369. Epub 2017 Oct 18.
• [2] Single-stranded DNA-binding proteins PURalpha and PURbeta bind to a purine-rich negative regulatory element of the alpha-myosin heavy chain gene and control transcriptional and translational regulation of the gene expression. Implications in the repression of alpha-myosin heavy chain during heart failure.J Biol Chem. 2003 Nov 7;278(45):44935-48. doi: 10.1074/jbc.M307696200. Epub 2003 Aug 21.
• [3] Deletions of PURA, at 5q31, and PURB, at 7p13, in myelodysplastic syndrome and progression to acute myelogenous leukemia.Leukemia. 2001 Jun;15(6):954-62. doi: 10.1038/sj.leu.2402108.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [6] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [9] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [10] 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.
• [11] Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach. BMC Syst Biol. 2012 Dec 10;6:152.
• [12] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [13] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [14] ST1926, a novel and orally active retinoid-related molecule inducing apoptosis in myeloid leukemia cells: modulation of intracellular calcium homeostasis. Blood. 2004 Jan 1;103(1):194-207.