Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTC7TNAX)

• DOT Name: Pleckstrin homology domain-containing family B member 1 (PLEKHB1)
• Synonyms: PH domain-containing family B member 1; Evectin-1; PH domain-containing protein in retina 1; PHRET1; Pleckstrin homology domain retinal protein 1
• Gene Name: PLEKHB1
• Related Disease:
  Breast cancer
  Breast carcinoma
  Glioblastoma multiforme
  leukaemia
  Leukemia
  Urinary tract infection
  Acute myelogenous leukaemia
  Neoplasm
• UniProt ID: PKHB1_HUMAN
• Pfam ID: PF00169
• Sequence:
  MSPAAPVPPDSALESPFEEMALVRGGWLWRQSSILRRWKRNWFALWLDGTLGYYHDETAQ
  DEEDRVLIHFNVRDIKIGPECHDVQPPEGRSRDGLLTVNLREGGRLHLCAETKDDALAWK
  TALLEANSTPAPAGATVPPRSRRVCSKVRCVTRSWSPCKVERRIWVRVYSPYQDYYEVVP
  PNAHEATYVRSYYGPPYAGPGVTHVIVREDPCYSAGAPLAMGMLAGAATGAALGSLMWSP
  CWF
• Tissue Specificity: Highly expressed in retina and brain. Levels are very low or not detectable in all other tissues tested.

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[2]
leukaemia	DISS7D1V	Strong	Biomarker	[3]
Leukemia	DISNAKFL	Strong	Biomarker	[3]
Urinary tract infection	DISMT6UV	Strong	Genetic Variation	[4]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[5]
Neoplasm	DISZKGEW	Limited	Biomarker	[6]

1 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 Pleckstrin homology domain-containing family B member 1 (PLEKHB1).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Pleckstrin homology domain-containing family B member 1 (PLEKHB1).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Pleckstrin homology domain-containing family B member 1 (PLEKHB1).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Pleckstrin homology domain-containing family B member 1 (PLEKHB1).	[10]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Pleckstrin homology domain-containing family B member 1 (PLEKHB1).	[11]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Pleckstrin homology domain-containing family B member 1 (PLEKHB1).	[10]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Pleckstrin homology domain-containing family B member 1 (PLEKHB1).	[12]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Pleckstrin homology domain-containing family B member 1 (PLEKHB1).	[13]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Pleckstrin homology domain-containing family B member 1 (PLEKHB1).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Pleckstrin homology domain-containing family B member 1 (PLEKHB1).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Pleckstrin homology domain-containing family B member 1 (PLEKHB1).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Pleckstrin homology domain-containing family B member 1 (PLEKHB1).	[16]

References

• [1] Paradoxical hormone responses of KPL-1 breast cancer cells in vivo: a significant role of angiogenesis in tumor growth.Oncology. 2000 Aug;59(2):158-65. doi: 10.1159/000012154.
• [2] Identification of genes differentially expressed in glioblastoma versus pilocytic astrocytoma using Suppression Subtractive Hybridization.Oncogene. 2006 May 4;25(19):2818-26. doi: 10.1038/sj.onc.1209305.
• [3] Functional characterization of L-selectin ligands on human neutrophils and leukemia cell lines: evidence for mucinlike ligand activity distinct from P-selectin glycoprotein ligand-1.Blood. 1998 Feb 1;91(3):1067-75.
• [4] Contribution of fucose-containing capsules in Klebsiella pneumoniae to bacterial virulence in mice.Exp Biol Med (Maywood). 2008 Jan;233(1):64-70. doi: 10.3181/0706-RM-170.
• [5] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [6] A radicicol derivative, KF58333, inhibits expression of hypoxia-inducible factor-1alpha and vascular endothelial growth factor, angiogenesis and growth of human breast cancer xenografts.Jpn J Cancer Res. 2001 Dec;92(12):1342-51. doi: 10.1111/j.1349-7006.2001.tb02159.x.
• [7] 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.
• [8] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [11] 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.
• [12] Pharmacogenomic identification of novel determinants of response to chemotherapy in colon cancer. Cancer Res. 2006 Mar 1;66(5):2765-77.
• [13] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [14] 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.
• [15] 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.
• [16] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.