Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTO4IVND)

• DOT Name: Mitotic-spindle organizing protein 1 (MZT1)
• Synonyms: Mitotic-spindle organizing protein associated with a ring of gamma-tubulin 1
• Gene Name: MZT1
• UniProt ID: MZT1_HUMAN
• PDB ID: 6L81; 6M33; 6X0U; 7AS4; 7QJ0; 7QJ1; 7QJ2; 7QJ3; 7QJ4; 7QJ5; 7QJ6; 7QJ7; 7QJ8; 7QJ9; 7QJA; 7QJB; 7QJC; 7QJD
• Pfam ID: PF12554
• Sequence:
  MASSSGAGAAAAAAAANLNAVRETMDVLLEISRILNTGLDMETLSICVRLCEQGINPEAL
  SSVIKELRKATEALKAAENMTS
• Function: Required for gamma-tubulin complex recruitment to the centrosome.
• Reactome Pathway:
  Recruitment of NuMA to mitotic centrosomes (R-HSA-380320)
  Recruitment of mitotic centrosome proteins and complexes (R-HSA-380270)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Mitotic-spindle organizing protein 1 (MZT1).	[1]

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 Mitotic-spindle organizing protein 1 (MZT1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Mitotic-spindle organizing protein 1 (MZT1).	[3]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Mitotic-spindle organizing protein 1 (MZT1).	[4]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Mitotic-spindle organizing protein 1 (MZT1).	[5]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Mitotic-spindle organizing protein 1 (MZT1).	[5]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Mitotic-spindle organizing protein 1 (MZT1).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Mitotic-spindle organizing protein 1 (MZT1).	[7]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 decreases the expression of Mitotic-spindle organizing protein 1 (MZT1).	[8]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Mitotic-spindle organizing protein 1 (MZT1).	[9]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Mitotic-spindle organizing protein 1 (MZT1).	[10]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Mitotic-spindle organizing protein 1 (MZT1).	[6]

References

• [1] 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.
• [2] 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.
• [3] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [4] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [5] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [6] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [7] 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.
• [8] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [9] 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.
• [10] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.