Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7XLMJ6)

• DOT Name: Metallophosphoesterase MPPED2 (MPPED2)
• Synonyms: EC 3.1.-.-; Fetal brain protein 239; 239FB; Metallophosphoesterase domain-containing protein 2
• Gene Name: MPPED2
• Related Disease:
  Neoplasm
  Migraine disorder
  Adenoma
  Colorectal carcinoma
  Dental caries
  Neuroblastoma
  Thyroid gland papillary carcinoma
• UniProt ID: MPPD2_HUMAN
• EC Number: 3.1.-.-
• Pfam ID: PF00149
• Sequence:
  MAHGIPSQGKVTITVDEYSSNPTQAFTHYNINQSRFQPPHVHMVDPIPYDTPKPAGHTRF
  VCISDTHSRTDGIQMPYGDILLHTGDFTELGLPSEVKKFNDWLGNLPYEYKIVIAGNHEL
  TFDKEFMADLVKQDYYRFPSVSKLKPEDFDNVQSLLTNSIYLQDSEVTVKGFRIYGAPWT
  PWFNGWGFNLPRGQSLLDKWNLIPEGIDILMTHGPPLGFRDWVPKELQRVGCVELLNTVQ
  RRVRPKLHVFGGIHEGYGIMTDGYTTYINASTCTVSFQPTNPPIIFDLPNPQGS
• Function: Displays low metallophosphoesterase activity (in vitro). May play a role in the development of the nervous system.
• Tissue Specificity: Expressed predominantly in fetal brain.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Biomarker	[1]
Migraine disorder	DISFCQTG	Strong	Genetic Variation	[2]
Adenoma	DIS78ZEV	moderate	Posttranslational Modification	[3]
Colorectal carcinoma	DIS5PYL0	moderate	Biomarker	[3]
Dental caries	DISRBCMD	Limited	Biomarker	[4]
Neuroblastoma	DISVZBI4	Limited	Altered Expression	[5]
Thyroid gland papillary carcinoma	DIS48YMM	Limited	Biomarker	[6]

2 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 Metallophosphoesterase MPPED2 (MPPED2).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Metallophosphoesterase MPPED2 (MPPED2).	[13]

8 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 Metallophosphoesterase MPPED2 (MPPED2).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Metallophosphoesterase MPPED2 (MPPED2).	[9]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Metallophosphoesterase MPPED2 (MPPED2).	[10]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Metallophosphoesterase MPPED2 (MPPED2).	[11]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Metallophosphoesterase MPPED2 (MPPED2).	[12]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Metallophosphoesterase MPPED2 (MPPED2).	[12]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Metallophosphoesterase MPPED2 (MPPED2).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Metallophosphoesterase MPPED2 (MPPED2).	[14]

References

• [1] Characterization of an evolutionarily conserved metallophosphoesterase that is expressed in the fetal brain and associated with the WAGR syndrome.J Biol Chem. 2009 Feb 20;284(8):5217-28. doi: 10.1074/jbc.M805996200. Epub 2008 Nov 12.
• [2] Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine.Nat Genet. 2016 Aug;48(8):856-66. doi: 10.1038/ng.3598. Epub 2016 Jun 20.
• [3] Genome-wide methylation profiling identified novel differentially hypermethylated biomarker MPPED2 in colorectal cancer.Clin Epigenetics. 2019 Mar 7;11(1):41. doi: 10.1186/s13148-019-0628-y.
• [4] Genetic Association of MPPED2 and ACTN2 with Dental Caries.J Dent Res. 2014 Jul;93(7):626-32. doi: 10.1177/0022034514534688. Epub 2014 May 8.
• [5] The metallophosphodiesterase Mpped2 impairs tumorigenesis in neuroblastoma.Cell Cycle. 2012 Feb 1;11(3):569-81. doi: 10.4161/cc.11.3.19063. Epub 2012 Feb 1.
• [6] Identification of Genes Associated with Papillary Thyroid Carcinoma (PTC) for Diagnosis by Integrated Analysis.Horm Metab Res. 2016 Apr;48(4):226-31. doi: 10.1055/s-0035-1569289. Epub 2016 Jan 12.
• [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] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [9] 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.
• [10] Gene expression profiling of human peri-implantation endometria between natural and stimulated cycles. Fertil Steril. 2008 Dec;90(6):2152-64.
• [11] 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.
• [12] 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.
• [13] 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.
• [14] 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.