Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDN45FN)

• DOT Name: Olfactomedin-like protein 3 (OLFML3)
• Synonyms: HNOEL-iso; hOLF44
• Gene Name: OLFML3
• Related Disease:
  Neoplasm
  Epilepsy
  Acute myelogenous leukaemia
• UniProt ID: OLFL3_HUMAN
• Pfam ID: PF02191
• Sequence:
  MGPSTPLLILFLLSWSGPLQGQQHHLVEYMERRLAALEERLAQCQDQSSRHAAELRDFKN
  KMLPLLEVAEKEREALRTEADTISGRVDRLEREVDYLETQNPALPCVEFDEKVTGGPGTK
  GKGRRNEKYDMVTDCGYTISQVRSMKILKRFGGPAGLWTKDPLGQTEKIYVLDGTQNDTA
  FVFPRLRDFTLAMAARKASRVRVPFPWVGTGQLVYGGFLYFARRPPGRPGGGGEMENTLQ
  LIKFHLANRTVVDSSVFPAEGLIPPYGLTADTYIDLAADEEGLWAVYATREDDRHLCLAK
  LDPQTLDTEQQWDTPCPRENAEAAFVICGTLYVVYNTRPASRARIQCSFDASGTLTPERA
  ALPYFPRRYGAHASLRYNPRERQLYAWDDGYQIVYKLEMRKKEEEV
• Function: Secreted scaffold protein that plays an essential role in dorsoventral patterning during early development. Stabilizes axial formation by restricting chordin (CHRD) activity on the dorsal side. Acts by facilitating the association between the tolloid proteases and their substrate chordin (CHRD), leading to enhance chordin (CHRD) degradation. May have matrix-related function involved in placental and embryonic development, or play a similar role in other physiological processes.
• Tissue Specificity: Abundant in placenta, moderate in liver and heart, whereas fairly weak in other tissues examined. On term placenta, mainly localized extracellularly surrounding the syncytiotrophoblastic cells and very rarely expressed in the maternal decidua layer.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Biomarker	[1]
Epilepsy	DISBB28L	Strong	Genetic Variation	[2]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[3]

31 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 Olfactomedin-like protein 3 (OLFML3).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Olfactomedin-like protein 3 (OLFML3).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Olfactomedin-like protein 3 (OLFML3).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Olfactomedin-like protein 3 (OLFML3).	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Olfactomedin-like protein 3 (OLFML3).	[8]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Olfactomedin-like protein 3 (OLFML3).	[9]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Olfactomedin-like protein 3 (OLFML3).	[10]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Olfactomedin-like protein 3 (OLFML3).	[11]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Olfactomedin-like protein 3 (OLFML3).	[12]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Olfactomedin-like protein 3 (OLFML3).	[13]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Olfactomedin-like protein 3 (OLFML3).	[14]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Olfactomedin-like protein 3 (OLFML3).	[15]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Olfactomedin-like protein 3 (OLFML3).	[12]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Olfactomedin-like protein 3 (OLFML3).	[16]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of Olfactomedin-like protein 3 (OLFML3).	[17]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Olfactomedin-like protein 3 (OLFML3).	[18]
Paclitaxel	DMLB81S	Approved	Paclitaxel increases the expression of Olfactomedin-like protein 3 (OLFML3).	[19]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol increases the expression of Olfactomedin-like protein 3 (OLFML3).	[20]
Testosterone Undecanoate	DMZO10Y	Approved	Testosterone Undecanoate decreases the expression of Olfactomedin-like protein 3 (OLFML3).	[21]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Olfactomedin-like protein 3 (OLFML3).	[22]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Olfactomedin-like protein 3 (OLFML3).	[12]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Olfactomedin-like protein 3 (OLFML3).	[16]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Olfactomedin-like protein 3 (OLFML3).	[8]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Olfactomedin-like protein 3 (OLFML3).	[23]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Olfactomedin-like protein 3 (OLFML3).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Olfactomedin-like protein 3 (OLFML3).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Olfactomedin-like protein 3 (OLFML3).	[24]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Olfactomedin-like protein 3 (OLFML3).	[25]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Olfactomedin-like protein 3 (OLFML3).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Olfactomedin-like protein 3 (OLFML3).	[26]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE decreases the expression of Olfactomedin-like protein 3 (OLFML3).	[9]

References

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• [2] A genome-wide association study of sodium levels and drug metabolism in an epilepsy cohort treated with carbamazepine and oxcarbazepine.Epilepsia Open. 2019 Jan 17;4(1):102-109. doi: 10.1002/epi4.12297. eCollection 2019 Mar.
• [3] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [4] 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.
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• [6] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [7] 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.
• [8] Convergent transcriptional profiles induced by endogenous estrogen and distinct xenoestrogens in breast cancer cells. Carcinogenesis. 2006 Aug;27(8):1567-78.
• [9] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [10] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [11] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [12] 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.
• [13] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [14] 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.
• [15] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [16] Gene expression profiling in Ishikawa cells: a fingerprint for estrogen active compounds. Toxicol Appl Pharmacol. 2009 Apr 1;236(1):85-96.
• [17] Gene expression signatures after ethanol exposure in differentiating embryoid bodies. Toxicol In Vitro. 2018 Feb;46:66-76.
• [18] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [19] Identification of selective inhibitors of cancer stem cells by high-throughput screening. Cell. 2009 Aug 21;138(4):645-659. doi: 10.1016/j.cell.2009.06.034. Epub 2009 Aug 13.
• [20] The genomic response of a human uterine endometrial adenocarcinoma cell line to 17alpha-ethynyl estradiol. Toxicol Sci. 2009 Jan;107(1):40-55.
• [21] Levonorgestrel enhances spermatogenesis suppression by testosterone with greater alteration in testicular gene expression in men. Biol Reprod. 2009 Mar;80(3):484-92.
• [22] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [23] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [24] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [25] 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.
• [26] 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.