Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1MOFLZ)

• DOT Name: Hematopoietic progenitor cell antigen CD34 (CD34)
• Synonyms: CD antigen CD34
• Gene Name: CD34
• UniProt ID: CD34_HUMAN
• Pfam ID: PF06365
• Sequence:
  MLVRRGARAGPRMPRGWTALCLLSLLPSGFMSLDNNGTATPELPTQGTFSNVSTNVSYQE
  TTTPSTLGSTSLHPVSQHGNEATTNITETTVKFTSTSVITSVYGNTNSSVQSQTSVISTV
  FTTPANVSTPETTLKPSLSPGNVSDLSTTSTSLATSPTKPYTSSSPILSDIKAEIKCSGI
  REVKLTQGICLEQNKTSSCAEFKKDRGEGLARVLCGEEQADADAGAQVCSLLLAQSEVRP
  QCLLLVLANRTEISSKLQLMKKHQSDLKKLGILDFTEQDVASHQSYSQKTLIALVTSGAL
  LAVLGITGYFLMNRRSWSPTGERLGEDPYYTENGGGQGYSSGPGTSPEAQGKASVNRGAQ
  ENGTGQATSRNGHSARQHVVADTEL
• Function: Possible adhesion molecule with a role in early hematopoiesis by mediating the attachment of stem cells to the bone marrow extracellular matrix or directly to stromal cells. Could act as a scaffold for the attachment of lineage specific glycans, allowing stem cells to bind to lectins expressed by stromal cells or other marrow components. Presents carbohydrate ligands to selectins.
• Tissue Specificity: Selectively expressed on hematopoietic progenitor cells and the small vessel endothelium of a variety of tissues.
• KEGG Pathway:
  Cell adhesion molecules (hsa04514)
  Hematopoietic cell lineage (hsa04640)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Hematopoietic progenitor cell antigen CD34 (CD34).	[1]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Hematopoietic progenitor cell antigen CD34 (CD34).	[2]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Hematopoietic progenitor cell antigen CD34 (CD34).	[3]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Hematopoietic progenitor cell antigen CD34 (CD34).	[4]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Hematopoietic progenitor cell antigen CD34 (CD34).	[5]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of Hematopoietic progenitor cell antigen CD34 (CD34).	[6]
Erythromycin	DM4K7GQ	Approved	Erythromycin increases the expression of Hematopoietic progenitor cell antigen CD34 (CD34).	[7]
Omacetaxine mepesuccinate	DMPU2WX	Approved	Omacetaxine mepesuccinate decreases the expression of Hematopoietic progenitor cell antigen CD34 (CD34).	[2]
Valsartan	DMREUQ6	Approved	Valsartan decreases the expression of Hematopoietic progenitor cell antigen CD34 (CD34).	[8]
Fenretinide	DMRD5SP	Phase 3	Fenretinide decreases the expression of Hematopoietic progenitor cell antigen CD34 (CD34).	[9]
Napabucasin	DMDZ6Q3	Phase 3	Napabucasin decreases the expression of Hematopoietic progenitor cell antigen CD34 (CD34).	[10]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Hematopoietic progenitor cell antigen CD34 (CD34).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Hematopoietic progenitor cell antigen CD34 (CD34).	[13]
Aminoguanidine	DMJQDUC	Phase 1	Aminoguanidine decreases the expression of Hematopoietic progenitor cell antigen CD34 (CD34).	[14]
Nitrobenzanthrone	DMN6L70	Investigative	Nitrobenzanthrone affects the expression of Hematopoietic progenitor cell antigen CD34 (CD34).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Hematopoietic progenitor cell antigen CD34 (CD34).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Hematopoietic progenitor cell antigen CD34 (CD34).	[15]

References

• [1] 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.
• [2] Synergistic killing effects of homoharringtonine and arsenic trioxide on acute myeloid leukemia stem cells and the underlying mechanisms. J Exp Clin Cancer Res. 2019 Jul 15;38(1):308. doi: 10.1186/s13046-019-1295-8.
• [3] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [4] Epigenetic activation of O-linked -N-acetylglucosamine transferase overrides the differentiation blockage in acute leukemia. EBioMedicine. 2020 Apr;54:102678. doi: 10.1016/j.ebiom.2020.102678. Epub 2020 Apr 6.
• [5] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [6] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [7] The in vitro effects of quinupristin/dalfopristin, erythromycin and levofloxacin at low concentrations on the expression of different cell adhesion molecules on the surface of endothelial cells (Eahy926). Toxicology. 2006 Jan 20;218(1):30-8. doi: 10.1016/j.tox.2005.09.014. Epub 2005 Nov 16.
• [8] Valsartan improves adipose tissue function in humans with impaired glucose metabolism: a randomized placebo-controlled double-blind trial. PLoS One. 2012;7(6):e39930. doi: 10.1371/journal.pone.0039930. Epub 2012 Jun 29.
• [9] The transforming growth factor-beta family members bone morphogenetic protein-2 and macrophage inhibitory cytokine-1 as mediators of the antiangiogenic activity of N-(4-hydroxyphenyl)retinamide. Clin Cancer Res. 2005 Jun 15;11(12):4610-9.
• [10] Suppression of cancer relapse and metastasis by inhibiting cancer stemness. Proc Natl Acad Sci U S A. 2015 Feb 10;112(6):1839-44. doi: 10.1073/pnas.1424171112. Epub 2015 Jan 20.
• [11] Arsenic exposure in utero exacerbates skin cancer response in adulthood with contemporaneous distortion of tumor stem cell dynamics. Cancer Res. 2008 Oct 15;68(20):8278-85. doi: 10.1158/0008-5472.CAN-08-2099.
• [12] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [13] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [14] Aminoguanidine impedes human pancreatic tumor growth and metastasis development in nude mice. World J Gastroenterol. 2009 Mar 7;15(9):1065-71.
• [15] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [16] 3-Nitrobenzanthrone promotes malignant transformation in human lung epithelial cells through the epiregulin-signaling pathway. Cell Biol Toxicol. 2022 Oct;38(5):865-887. doi: 10.1007/s10565-021-09612-1. Epub 2021 May 25.