Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXAO193)

• DOT Name: Melanoma-associated antigen 1 (MAGEA1)
• Synonyms: Antigen MZ2-E; Cancer/testis antigen 1.1; CT1.1; MAGE-1 antigen
• Gene Name: MAGEA1
• UniProt ID: MAGA1_HUMAN
• PDB ID: 1W72; 3BO8
• Pfam ID: PF01454 ; PF12440
• Sequence:
  MSLEQRSLHCKPEEALEAQQEALGLVCVQAATSSSSPLVLGTLEEVPTAGSTDPPQSPQG
  ASAFPTTINFTRQRQPSEGSSSREEEGPSTSCILESLFRAVITKKVADLVGFLLLKYRAR
  EPVTKAEMLESVIKNYKHCFPEIFGKASESLQLVFGIDVKEADPTGHSYVLVTCLGLSYD
  GLLGDNQIMPKTGFLIIVLVMIAMEGGHAPEEEIWEELSVMEVYDGREHSAYGEPRKLLT
  QDLVQEKYLEYRQVPDSDPARYEFLWGPRALAETSYVKVLEYVIKVSARVRFFFPSLREA
  ALREEEEGV
• Function: May be involved in transcriptional regulation through interaction with SNW1 and recruiting histone deactelyase HDAC1. May inhibit notch intracellular domain (NICD) transactivation. May play a role in embryonal development and tumor transformation or aspects of tumor progression. Antigen recognized on a melanoma by autologous cytolytic T-lymphocytes.
• Tissue Specificity: Expressed in many tumors of several types, such as melanoma, head and neck squamous cell carcinoma, lung carcinoma and breast carcinoma, but not in normal tissues except for testes. Never expressed in kidney tumors, leukemias and lymphomas.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Melanoma-associated antigen 1 (MAGEA1).	[1]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Melanoma-associated antigen 1 (MAGEA1).	[2]
Vemurafenib	DM62UG5	Approved	Vemurafenib decreases the expression of Melanoma-associated antigen 1 (MAGEA1).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of Melanoma-associated antigen 1 (MAGEA1).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Decitabine	DMQL8XJ	Approved	Decitabine decreases the methylation of Melanoma-associated antigen 1 (MAGEA1).	[3]
Azacitidine	DMTA5OE	Approved	Azacitidine decreases the methylation of Melanoma-associated antigen 1 (MAGEA1).	[3]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Melanoma-associated antigen 1 (MAGEA1).	[6]

References

• [1] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [2] 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.
• [3] Hydroxycarbamide in combination with azacitidine or decitabine is antagonistic on DNA methylation inhibition. Br J Haematol. 2007 Sep;138(5):616-23. doi: 10.1111/j.1365-2141.2007.06707.x.
• [4] PLX4032 Mediated Melanoma Associated Antigen Potentiation in Patient Derived Primary Melanoma Cells. J Cancer. 2015 Oct 29;6(12):1320-30. doi: 10.7150/jca.11126. eCollection 2015.
• [5] Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014 Dec;775-776:48-54. doi: 10.1016/j.mrgentox.2014.10.011. Epub 2014 Nov 4.
• [6] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.