Details of Drug Off-Target (DOT)

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

• DOT Name: Polypyrimidine tract-binding protein 3 (PTBP3)
• Synonyms: Regulator of differentiation 1; Rod1
• Gene Name: PTBP3
• Related Disease:
  Advanced cancer
  Colorectal carcinoma
  Neoplasm
  Adult glioblastoma
  Gastric cancer
  Glioblastoma multiforme
  Stomach cancer
  Breast cancer
  Breast carcinoma
  Hepatocellular carcinoma
• UniProt ID: PTBP3_HUMAN
• Pfam ID: PF13893 ; PF11835
• Sequence:
  MDGVVTDLITVGLKRGSDELLSSGIINGPFTMNSSTPSTANGNDSKKFKRDRPPCSPSRV
  LHLRKIPCDVTEAEIISLGLPFGKVTNLLMLKGKSQAFLEMASEEAAVTMVNYYTPITPH
  LRSQPVYIQYSNHRELKTDNLPNQARAQAALQAVSAVQSGSLALSGGPSNEGTVLPGQSP
  VLRIIIENLFYPVTLEVLHQIFSKFGTVLKIITFTKNNQFQALLQYADPVNAHYAKMALD
  GQNIYNACCTLRIDFSKLTSLNVKYNNDKSRDFTRLDLPTGDGQPSLEPPMAAAFGAPGI
  ISSPYAGAAGFAPAIGFPQATGLSVPAVPGALGPLTITSSAVTGRMAIPGASGIPGNSVL
  LVTNLNPDLITPHGLFILFGVYGDVHRVKIMFNKKENALVQMADANQAQLAMNHLSGQRL
  YGKVLRATLSKHQAVQLPREGQEDQGLTKDFSNSPLHRFKKPGSKNFQNIFPPSATLHLS
  NIPPSVTVDDLKNLFIEAGCSVKAFKFFQKDRKMALIQLGSVEEAIQALIELHNHDLGEN
  HHLRVSFSKSTI
• Function: RNA-binding protein that mediates pre-mRNA alternative splicing regulation. Plays a role in the regulation of cell proliferation, differentiation and migration. Positive regulator of EPO-dependent erythropoiesis. Participates in cell differentiation regulation by repressing tissue-specific exons. Promotes FAS exon 6 skipping. Binds RNA, preferentially to both poly(G) and poly(U).
• Tissue Specificity: Expressed in several hematopoietic cell lines examined.

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Adult glioblastoma	DISVP4LU	moderate	Biomarker	[3]
Gastric cancer	DISXGOUK	moderate	Biomarker	[4]
Glioblastoma multiforme	DISK8246	moderate	Biomarker	[3]
Stomach cancer	DISKIJSX	moderate	Biomarker	[4]
Breast cancer	DIS7DPX1	Disputed	Altered Expression	[1]
Breast carcinoma	DIS2UE88	Disputed	Altered Expression	[1]
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[5]

11 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 Polypyrimidine tract-binding protein 3 (PTBP3).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Polypyrimidine tract-binding protein 3 (PTBP3).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Polypyrimidine tract-binding protein 3 (PTBP3).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Polypyrimidine tract-binding protein 3 (PTBP3).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Polypyrimidine tract-binding protein 3 (PTBP3).	[10]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Polypyrimidine tract-binding protein 3 (PTBP3).	[11]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Polypyrimidine tract-binding protein 3 (PTBP3).	[12]
Marinol	DM70IK5	Approved	Marinol increases the expression of Polypyrimidine tract-binding protein 3 (PTBP3).	[13]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Polypyrimidine tract-binding protein 3 (PTBP3).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Polypyrimidine tract-binding protein 3 (PTBP3).	[16]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Polypyrimidine tract-binding protein 3 (PTBP3).	[17]

1 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 decreases the phosphorylation of Polypyrimidine tract-binding protein 3 (PTBP3).	[14]

References

• [1] PTBP3-Mediated Regulation of ZEB1 mRNA Stability Promotes Epithelial-Mesenchymal Transition in Breast Cancer.Cancer Res. 2018 Jan 15;78(2):387-398. doi: 10.1158/0008-5472.CAN-17-0883. Epub 2017 Nov 29.
• [2] PTBP3 contributes to colorectal cancer growth and metastasis via translational activation of HIF-1.J Exp Clin Cancer Res. 2019 Jul 10;38(1):301. doi: 10.1186/s13046-019-1312-y.
• [3] MicroRNA-210 regulates cell proliferation and apoptosis by targeting regulator of differentiation 1 in glioblastoma cells.Folia Neuropathol. 2015;53(3):236-44. doi: 10.5114/fn.2015.54424.
• [4] PTBP3 contributes to the metastasis of gastric cancer by mediating CAV1 alternative splicing.Cell Death Dis. 2018 May 1;9(5):569. doi: 10.1038/s41419-018-0608-8.
• [5] PTBP3 splicing factor promotes hepatocellular carcinoma by destroying the splicing balance of NEAT1 and pre-miR-612.Oncogene. 2018 Dec;37(50):6399-6413. doi: 10.1038/s41388-018-0416-8. Epub 2018 Aug 1.
• [6] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [7] 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.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [10] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [11] An approach to elucidate potential mechanism of renal toxicity of arsenic trioxide. Exp Hematol. 2007 Feb;35(2):252-62.
• [12] 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.
• [13] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [14] 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.
• [15] 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.
• [16] 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.
• [17] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.