Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTF5YBQG)

• DOT Name: Paraneoplastic antigen Ma2 (PNMA2)
• Synonyms: 40 kDa neuronal protein; Onconeuronal antigen Ma2; Paraneoplastic neuronal antigen MM2
• Gene Name: PNMA2
• Related Disease: Achalasia
• UniProt ID: PNMA2_HUMAN
• Pfam ID: PF14893 ; PF20846
• Sequence:
  MALALLEDWCRIMSVDEQKSLMVTGIPADFEEAEIQEVLQETLKSLGRYRLLGKIFRKQE
  NANAVLLELLEDTDVSAIPSEVQGKGGVWKVIFKTPNQDTEFLERLNLFLEKEGQTVSGM
  FRALGQEGVSPATVPCISPELLAHLLGQAMAHAPQPLLPMRYRKLRVFSGSAVPAPEEES
  FEVWLEQATEIVKEWPVTEAEKKRWLAESLRGPALDLMHIVQADNPSISVEECLEAFKQV
  FGSLESRRTAQVRYLKTYQEEGEKVSAYVLRLETLLRRAVEKRAIPRRIADQVRLEQVMA
  GATLNQMLWCRLRELKDQGPPPSFLELMKVIREEEEEEASFENESIEEPEERDGYGRWNH
  EGDD
• Tissue Specificity: Brain-specific. In some cancer patients, specifically expressed by testicular tumor cells.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Achalasia	DISK845N	Strong	Biomarker	[1]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Paraneoplastic antigen Ma2 (PNMA2) affects the response to substance of Methotrexate.	[11]
Fluorouracil	DMUM7HZ	Approved	Paraneoplastic antigen Ma2 (PNMA2) affects the response to substance of Fluorouracil.	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Paraneoplastic antigen Ma2 (PNMA2).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Paraneoplastic antigen Ma2 (PNMA2).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Paraneoplastic antigen Ma2 (PNMA2).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Paraneoplastic antigen Ma2 (PNMA2).	[5]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Paraneoplastic antigen Ma2 (PNMA2).	[6]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Paraneoplastic antigen Ma2 (PNMA2).	[5]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Paraneoplastic antigen Ma2 (PNMA2).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Paraneoplastic antigen Ma2 (PNMA2).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Paraneoplastic antigen Ma2 (PNMA2).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Paraneoplastic antigen Ma2 (PNMA2).	[10]

References

• [1] Gelatinase B/Matrix Metalloproteinase-9 as Innate Immune Effector Molecule in Achalasia.Clin Transl Gastroenterol. 2018 Nov 19;9(11):208. doi: 10.1038/s41424-018-0076-6.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] 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.
• [4] 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.
• [5] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [6] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [7] 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.
• [8] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [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] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [11] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.