Details of Drug Off-Target (DOT)

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

• DOT Name: Noelin-3 (OLFM3)
• Synonyms: Olfactomedin-3; Optimedin
• Gene Name: OLFM3
• Related Disease:
  Multiple sclerosis
  Squamous cell carcinoma
• UniProt ID: NOE3_HUMAN
• Pfam ID: PF12308 ; PF02191
• Sequence:
  MSPPLLKLGAVLSTMAMISNWMSQTLPSLVGLNTTRLSTPDTLTQISPKEGWQVYSSAQD
  PDGRCICTVVAPEQNLCSRDAKSRQLRQLLEKVQNMSQSIEVLNLRTQRDFQYVLKMETQ
  MKGLKAKFRQIEDDRKTLMTKHFQELKEKMDELLPLIPVLEQYKTDAKLITQFKEEIRNL
  SAVLTGIQEEIGAYDYEELHQRVLSLETRLRDCMKKLTCGKLMKITGPVTVKTSGTRFGA
  WMTDPLASEKNNRVWYMDSYTNNKIVREYKSIADFVSGAESRTYNLPFKWAGTNHVVYNG
  SLYFNKYQSNIIIKYSFDMGRVLAQRSLEYAGFHNVYPYTWGGFSDIDLMADEIGLWAVY
  ATNQNAGNIVISQLNQDTLEVMKSWSTGYPKRSAGESFMICGTLYVTNSHLTGAKVYYSY
  STKTSTYEYTDIPFHNQYFHISMLDYNARDRALYAWNNGHQVLFNVTLFHIIKTEDDT
• Tissue Specificity: In the eye, expressed in trabecular meshwork and neural retina; in non-ocular tissues, expressed in brain and lung.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Multiple sclerosis	DISB2WZI	Strong	Genetic Variation	[1]
Squamous cell carcinoma	DISQVIFL	moderate	Altered Expression	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Noelin-3 (OLFM3).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Noelin-3 (OLFM3).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Noelin-3 (OLFM3).	[5]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Noelin-3 (OLFM3).	[6]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Noelin-3 (OLFM3).	[7]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Noelin-3 (OLFM3).	[7]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Noelin-3 (OLFM3).	[7]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Noelin-3 (OLFM3).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of Noelin-3 (OLFM3).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Noelin-3 (OLFM3).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Noelin-3 (OLFM3).	[8]

References

• [1] Identification of a novel Parkinson's disease locus via stratified genome-wide association study.BMC Genomics. 2014 Feb 10;15:118. doi: 10.1186/1471-2164-15-118.
• [2] Olfactomedin III expression contributes to anoikis-resistance in clonal variants of a human lung squamous carcinoma cell line.Exp Cell Res. 2012 Mar 10;318(5):593-602. doi: 10.1016/j.yexcr.2012.01.012. Epub 2012 Jan 13.
• [3] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [4] 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.
• [5] 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.
• [6] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [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] 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.
• [9] 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.
• [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.