Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTO3F7B0)

• DOT Name: Paraneoplastic antigen-like protein 8A (PNMA8A)
• Synonyms: PNMA-like protein 1
• Gene Name: PNMA8A
• UniProt ID: PNM8A_HUMAN
• Pfam ID: PF20847 ; PF20846
• Sequence:
  MSKTMAMNLLEDWCRGMEVDIHRSLLVTGIPEDCGQAEIEETLNGVLSPLGPYRVLNKIF
  VREENVKAALIEVGEGVNLSTIPREFPGRGGVWRVVCRDPTQDAEFLKNLNEFLDAEGRT
  WEDVVRLLQLNHPTLSQNQHQPPENWAEALGVLLGAVVQIIFCMDAEIRSREEARAQEAA
  EFEEMAAWALAAGRKVKKEPGLAAEVGSALKAETPNNWNATEDQHEPTKPLVRRAGAKSR
  SRRKKQKKNSRQEAVPWKKPKGINSNSTANLEDPEVGDAESMAISEPIKGSRKPCVNKEE
  LALKKPMAKCAWKGPREPPQDARAEAESPGGASESDQDGGHESPPKKKAVAWVSAKNPAP
  MRKKKKVSLGPVSYVLVDSEDGRKKPVMPKKGPGSRREASDQKAPRGQQPAEATASTSRG
  PKAKPEGSPRRATNESRKV

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Topotecan	DMP6G8T	Approved	Paraneoplastic antigen-like protein 8A (PNMA8A) affects the response to substance of Topotecan.	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Paraneoplastic antigen-like protein 8A (PNMA8A).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Paraneoplastic antigen-like protein 8A (PNMA8A).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Paraneoplastic antigen-like protein 8A (PNMA8A).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Paraneoplastic antigen-like protein 8A (PNMA8A).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Paraneoplastic antigen-like protein 8A (PNMA8A).	[4]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Paraneoplastic antigen-like protein 8A (PNMA8A).	[4]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Paraneoplastic antigen-like protein 8A (PNMA8A).	[5]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Paraneoplastic antigen-like protein 8A (PNMA8A).	[7]

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] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [3] 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.
• [4] 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.
• [5] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [6] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [7] 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.
• [8] 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.