Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTO26804)

• DOT Name: Myb/SANT-like DNA-binding domain-containing protein 3 (MSANTD3)
• Gene Name: MSANTD3
• Related Disease: Acinar cell carcinoma
• UniProt ID: MSD3_HUMAN
• Pfam ID: PF13873
• Sequence:
  MQNNEIIKPAKYFSELEKSILLALVEKYKYVLECKKSDARTIALKQRTWQALAHEYNSQP
  SVSLRDFKQLKKCWENIKARTKKIMAHERREKVKRSVSPLLSTHVLGKEKIASMLPEQLY
  FLQSPPEEEPEYHPDASAQESFAVSNRELCDDEKEFIHFPVCEGTSQPEPSCSAVRITAN
  KNYRSKTSQEGALKKMHEEEHHQQMSILQLQLIQMNEVHVAKIQQIERECEMAEEEHRIK
  MEVLNKKKMYWERKLQTFTKEWPVSSFNRPFPNSP
• Tissue Specificity: Expressed in brain.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acinar cell carcinoma	DIS37Y0J	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Myb/SANT-like DNA-binding domain-containing protein 3 (MSANTD3).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Myb/SANT-like DNA-binding domain-containing protein 3 (MSANTD3).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Myb/SANT-like DNA-binding domain-containing protein 3 (MSANTD3).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Myb/SANT-like DNA-binding domain-containing protein 3 (MSANTD3).	[3]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Myb/SANT-like DNA-binding domain-containing protein 3 (MSANTD3).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Myb/SANT-like DNA-binding domain-containing protein 3 (MSANTD3).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Myb/SANT-like DNA-binding domain-containing protein 3 (MSANTD3).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Myb/SANT-like DNA-binding domain-containing protein 3 (MSANTD3).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Myb/SANT-like DNA-binding domain-containing protein 3 (MSANTD3).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Myb/SANT-like DNA-binding domain-containing protein 3 (MSANTD3).	[8]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Myb/SANT-like DNA-binding domain-containing protein 3 (MSANTD3).	[10]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Myb/SANT-like DNA-binding domain-containing protein 3 (MSANTD3).	[10]

References

• [1] The HTN3-MSANTD3 Fusion Gene Defines a Subset of Acinic Cell Carcinoma of the Salivary Gland.Am J Surg Pathol. 2019 Apr;43(4):489-496. doi: 10.1097/PAS.0000000000001200.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [6] 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.
• [7] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [8] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [9] 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.
• [10] 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.
• [11] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.