Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKNYMU2)

• DOT Name: Annexin A9 (ANXA9)
• Synonyms: Annexin XXXI; Annexin-31; Annexin-9; Pemphaxin
• Gene Name: ANXA9
• Related Disease:
  Colorectal carcinoma
  Melanoma
  Neoplasm
  Squamous cell carcinoma
• UniProt ID: ANXA9_HUMAN
• Pfam ID: PF00191
• Sequence:
  MSVTGGKMAPSLTQEILSHLGLASKTAAWGTLGTLRTFLNFSVDKDAQRLLRAITGQGVD
  RSAIVDVLTNRSREQRQLISRNFQERTQQDLMKSLQAALSGNLERIVMALLQPTAQFDAQ
  ELRTALKASDSAVDVAIEILATRTPPQLQECLAVYKHNFQVEAVDDITSETSGILQDLLL
  ALAKGGRDSYSGIIDYNLAEQDVQALQRAEGPSREETWVPVFTQRNPEHLIRVFDQYQRS
  TGQELEEAVQNRFHGDAQVALLGLASVIKNTPLYFADKLHQALQETEPNYQVLIRILISR
  CETDLLSIRAEFRKKFGKSLYSSLQDAVKGDCQSALLALCRAEDM
• Function: Low affinity receptor for acetylcholine known to be targeted by disease-causing pemphigus vulgaris antibodies in keratinocytes.
• Tissue Specificity: Expressed in the stratified squamous skin epithelium, but not in epithelia of other types (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[1]
Melanoma	DIS1RRCY	Strong	Genetic Variation	[2]
Neoplasm	DISZKGEW	Limited	Altered Expression	[3]
Squamous cell carcinoma	DISQVIFL	Limited	Biomarker	[3]

1 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 Annexin A9 (ANXA9).	[4]

12 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 Annexin A9 (ANXA9).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Annexin A9 (ANXA9).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Annexin A9 (ANXA9).	[7]
Amphotericin B	DMTAJQE	Approved	Amphotericin B decreases the expression of Annexin A9 (ANXA9).	[8]
Ibuprofen	DM8VCBE	Approved	Ibuprofen decreases the expression of Annexin A9 (ANXA9).	[9]
Rofecoxib	DM3P5DA	Approved	Rofecoxib decreases the expression of Annexin A9 (ANXA9).	[9]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Annexin A9 (ANXA9).	[10]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Annexin A9 (ANXA9).	[11]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of Annexin A9 (ANXA9).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Annexin A9 (ANXA9).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Annexin A9 (ANXA9).	[14]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Annexin A9 (ANXA9).	[15]

References

• [1] Annexin A9 promotes invasion and metastasis of colorectal cancer and predicts poor prognosis.Int J Mol Med. 2018 Apr;41(4):2185-2192. doi: 10.3892/ijmm.2018.3432. Epub 2018 Jan 29.
• [2] Genome-wide association study identifies novel loci predisposing to cutaneous melanoma.Hum Mol Genet. 2011 Dec 15;20(24):5012-23. doi: 10.1093/hmg/ddr415. Epub 2011 Sep 17.
• [3] Frequent Alteration of Annexin A9 and A10 in HPV-Negative Head and Neck Squamous Cell Carcinomas: Correlation with the Histopathological Differentiation Grade.J Clin Med. 2019 Feb 10;8(2):229. doi: 10.3390/jcm8020229.
• [4] Integrated 'omics analysis reveals new drug-induced mitochondrial perturbations in human hepatocytes. Toxicol Lett. 2018 Jun 1;289:1-13.
• [5] 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.
• [6] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Differential expression of microRNAs and their predicted targets in renal cells exposed to amphotericin B and its complex with copper (II) ions. Toxicol Mech Methods. 2017 Sep;27(7):537-543. doi: 10.1080/15376516.2017.1333554. Epub 2017 Jun 8.
• [9] Rofecoxib modulates multiple gene expression pathways in a clinical model of acute inflammatory pain. Pain. 2007 Mar;128(1-2):136-47.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [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.
• [12] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [13] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [14] 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.
• [15] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.