Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCTKR47)

• DOT Name: Myeloid cell nuclear differentiation antigen (MNDA)
• Gene Name: MNDA
• Related Disease:
  Abdominal aortic aneurysm
  Atherosclerosis
  B-cell neoplasm
  Bone osteosarcoma
  Chromosomal disorder
  MALT lymphoma
  Myelodysplastic syndrome
  Osteosarcoma
  Lymphoma
  Nodal marginal zone lymphoma
  Small lymphocytic lymphoma
  Acute myelogenous leukaemia
  AIDS-related lymphoma
  Childhood myelodysplastic syndrome
  Chronic myelogenous leukaemia
  Follicular lymphoma
  Kaposi sarcoma
  leukaemia
  Leukemia
  Marginal zone lymphoma
  Type-1 diabetes
• UniProt ID: MNDA_HUMAN
• PDB ID: 2DBG; 5H7Q; 5WPZ; 8I6K
• Pfam ID: PF02760 ; PF02758
• Sequence:
  MVNEYKKILLLKGFELMDDYHFTSIKSLLAYDLGLTTKMQEEYNRIKITDLMEKKFQGVA
  CLDKLIELAKDMPSLKNLVNNLRKEKSKVAKKIKTQEKAPVKKINQEEVGLAAPAPTARN
  KLTSEARGRIPVAQKRKTPNKEKTEAKRNKVSQEQSKPPGPSGASTSAAVDHPPLPQTSS
  STPSNTSFTPNQETQAQRQVDARRNVPQNDPVTVVVLKATAPFKYESPENGKSTMFHATV
  ASKTQYFHVKVFDINLKEKFVRKKVITISDYSECKGVMEIKEASSVSDFNQNFEVPNRII
  EIANKTPKISQLYKQASGTMVYGLFMLQKKSVHKKNTIYEIQDNTGSMDVVGSGKWHNIK
  CEKGDKLRLFCLQLRTVDRKLKLVCGSHSFIKVIKAKKNKEGPMNVN
• Function: May act as a transcriptional activator/repressor in the myeloid lineage. Plays a role in the granulocyte/monocyte cell-specific response to interferon. Stimulates the DNA binding of the transcriptional repressor protein YY1.
• Tissue Specificity: Expressed constitutively in cells of the myeloid lineage. Found in promyelocyte stage cells as well as in all other stage cells including peripheral blood monocytes and granulocytes. Also appears in myeloblast cells in some cases of acute myeloid Leukemia.
• Reactome Pathway: Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

21 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Abdominal aortic aneurysm	DISD06OF	Strong	Biomarker	[1]
Atherosclerosis	DISMN9J3	Strong	Genetic Variation	[2]
B-cell neoplasm	DISVY326	Strong	Biomarker	[3]
Bone osteosarcoma	DIST1004	Strong	Altered Expression	[4]
Chromosomal disorder	DISM5BB5	Strong	Biomarker	[5]
MALT lymphoma	DIS1AVVE	Strong	Biomarker	[3]
Myelodysplastic syndrome	DISYHNUI	Strong	Altered Expression	[6]
Osteosarcoma	DISLQ7E2	Strong	Altered Expression	[4]
Lymphoma	DISN6V4S	moderate	Altered Expression	[7]
Nodal marginal zone lymphoma	DIS7MP4T	moderate	Altered Expression	[7]
Small lymphocytic lymphoma	DIS30POX	moderate	Altered Expression	[7]
Acute myelogenous leukaemia	DISCSPTN	Limited	Biomarker	[8]
AIDS-related lymphoma	DISSLRAU	Limited	Altered Expression	[9]
Childhood myelodysplastic syndrome	DISMN80I	Limited	Biomarker	[8]
Chronic myelogenous leukaemia	DIS0301E	Limited	Altered Expression	[10]
Follicular lymphoma	DISVEUR6	Limited	Biomarker	[5]
Kaposi sarcoma	DISC1H1Z	Limited	Biomarker	[9]
leukaemia	DISS7D1V	Limited	Altered Expression	[10]
Leukemia	DISNAKFL	Limited	Altered Expression	[10]
Marginal zone lymphoma	DISLZ4AO	Limited	Biomarker	[3]
Type-1 diabetes	DIS7HLUB	Limited	Altered Expression	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Myeloid cell nuclear differentiation antigen (MNDA).	[12]
Coprexa	DMA0WEK	Phase 3	Coprexa increases the expression of Myeloid cell nuclear differentiation antigen (MNDA).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Myeloid cell nuclear differentiation antigen (MNDA).	[14]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Myeloid cell nuclear differentiation antigen (MNDA).	[16]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the expression of Myeloid cell nuclear differentiation antigen (MNDA).	[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 increases the phosphorylation of Myeloid cell nuclear differentiation antigen (MNDA).	[15]

References

• [1] Simultaneous analysis of 1176 gene products in normal human aorta and abdominal aortic aneurysms using a membrane-based complementary DNA expression array.J Vasc Surg. 2001 Jul;34(1):143-50. doi: 10.1067/mva.2001.113310.
• [2] Variable expression of human myeloid specific nuclear antigen MNDA in monocyte lineage cells in atherosclerosis.J Cell Biochem. 2005 May 15;95(2):293-301. doi: 10.1002/jcb.20435.
• [3] Myeloid Cell Nuclear Differentiation Antigen (MNDA) Positivity in Primary Follicles: Potential Pitfall in the Differential Diagnosis With Marginal Zone Lymphoma.Appl Immunohistochem Mol Morphol. 2020 May/Jun;28(5):384-388. doi: 10.1097/PAI.0000000000000738.
• [4] Hsa-miR-889-3p promotes the proliferation of osteosarcoma through inhibiting myeloid cell nuclear differentiation antigen expression.Biomed Pharmacother. 2019 Jun;114:108819. doi: 10.1016/j.biopha.2019.108819. Epub 2019 Apr 2.
• [5] Diagnostic value of STMN1, LMO2, HGAL, AID expression and 1p36 chromosomal abnormalities in primary cutaneous B cell lymphomas.Histopathology. 2017 Oct;71(4):648-660. doi: 10.1111/his.13279. Epub 2017 Jul 19.
• [6] Dysregulated human myeloid nuclear differentiation antigen expression in myelodysplastic syndromes: evidence for a role in apoptosis.Cancer Res. 2006 May 1;66(9):4645-51. doi: 10.1158/0008-5472.CAN-06-0229.
• [7] Identification of MNDA as a new marker for nodal marginal zone lymphoma.Leukemia. 2009 Oct;23(10):1847-57. doi: 10.1038/leu.2009.108. Epub 2009 May 28.
• [8] MNDA binds NPM/B23 and the NPM-MLF1 chimera generated by the t(3;5) associated with myelodysplastic syndrome and acute myeloid leukemia.Exp Hematol. 1997 Oct;25(11):1111-7.
• [9] Latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus interacts with human myeloid cell nuclear differentiation antigen induced by interferon alpha.Virus Genes. 2003 Dec;27(3):237-47. doi: 10.1023/a:1026391715071.
• [10] Regulation and specificity of MNDA expression in monocytes, macrophages, and leukemia/B lymphoma cell lines.J Cell Biochem. 1994 Dec;56(4):559-67. doi: 10.1002/jcb.240560417.
• [11] The expression of inflammatory genes is upregulated in peripheral blood of patients with type 1 diabetes.Diabetes Care. 2013 Sep;36(9):2794-802. doi: 10.2337/dc12-1986. Epub 2013 May 1.
• [12] Pharmacogenomic analysis of acute promyelocytic leukemia cells highlights CYP26 cytochrome metabolism in differential all-trans retinoic acid sensitivity. Blood. 2007 May 15;109(10):4450-60.
• [13] Copper deprivation enhances the chemosensitivity of pancreatic cancer to rapamycin by mTORC1/2 inhibition. Chem Biol Interact. 2023 Sep 1;382:110546. doi: 10.1016/j.cbi.2023.110546. Epub 2023 Jun 7.
• [14] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [15] 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.
• [16] Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.
• [17] Microarray analysis of H2O2-, HNE-, or tBH-treated ARPE-19 cells. Free Radic Biol Med. 2002 Nov 15;33(10):1419-32.