Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDQWTY4)

• DOT Name: Multiple epidermal growth factor-like domains protein 9 (MEGF9)
• Synonyms: Multiple EGF-like domains protein 9; Epidermal growth factor-like protein 5; EGF-like protein 5
• Gene Name: MEGF9
• Related Disease:
  Acute myelogenous leukaemia
  Breast cancer
  Breast carcinoma
  Neoplasm
• UniProt ID: MEGF9_HUMAN
• Pfam ID: PF00053
• Sequence:
  MNGGAERAMRSLPSLGGLALLCCAAAAAAAAVASAASAGNVTGGGGAAGQVDASPGPGLR
  GEPSHPFPRATAPTAQAPRTGPPRATVHRPLAATSPAQSPETTPLWATAGPSSTTFQAPL
  GPSPTTPPAAERTSTTSQAPTRPAPTTLSTTTGPAPTTPVATTVPAPTTPRTPTPDLPSS
  SNSSVLPTPPATEAPSSPPPEYVCNCSVVGSLNVNRCNQTTGQCECRPGYQGLHCETCKE
  GFYLNYTSGLCQPCDCSPHGALSIPCNSSGKCQCKVGVIGSICDRCQDGYYGFSKNGCLP
  CQCNNRSASCDALTGACLNCQENSKGNHCEECKEGFYQSPDATKECLRCPCSAVTSTGSC
  SIKSSELEPECDQCKDGYIGPNCNKCENGYYNFDSICRKCQCHGHVDPVKTPKICKPESG
  ECINCLHNTTGFWCENCLEGYVHDLEGNCIKKEVILPTPEGSTILVSNASLTTSVPTPVI
  NSTFTPTTLQTIFSVSTSENSTSALADVSWTQFNIIILTVIIIVVVLLMGFVGAVYMYRE
  YQNRKLNAPFWTIELKEDNISFSSYHDSIPNADVSGLLEDDGNEVAPNGQLTLTTPIHNY
  KA

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[1]
Breast cancer	DIS7DPX1	moderate	Biomarker	[2]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[2]
Neoplasm	DISZKGEW	moderate	Altered Expression	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Multiple epidermal growth factor-like domains protein 9 (MEGF9) affects the response to substance of Methotrexate.	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Multiple epidermal growth factor-like domains protein 9 (MEGF9).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Multiple epidermal growth factor-like domains protein 9 (MEGF9).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Multiple epidermal growth factor-like domains protein 9 (MEGF9).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Multiple epidermal growth factor-like domains protein 9 (MEGF9).	[6]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Multiple epidermal growth factor-like domains protein 9 (MEGF9).	[7]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene decreases the expression of Multiple epidermal growth factor-like domains protein 9 (MEGF9).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Multiple epidermal growth factor-like domains protein 9 (MEGF9).	[10]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Multiple epidermal growth factor-like domains protein 9 (MEGF9).	[11]
Bilirubin	DMI0V4O	Investigative	Bilirubin decreases the expression of Multiple epidermal growth factor-like domains protein 9 (MEGF9).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Multiple epidermal growth factor-like domains protein 9 (MEGF9).	[9]

References

• [1] 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.
• [2] miR-125b acts as a tumor suppressor in breast tumorigenesis via its novel direct targets ENPEP, CK2-, CCNJ, and MEGF9.PLoS One. 2013 Oct 3;8(10):e76247. doi: 10.1371/journal.pone.0076247. eCollection 2013.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [5] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [6] 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.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] Gene expression preferentially regulated by tamoxifen in breast cancer cells and correlations with clinical outcome. Cancer Res. 2006 Jul 15;66(14):7334-40.
• [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] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [11] Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.
• [12] Global changes in gene regulation demonstrate that unconjugated bilirubin is able to upregulate and activate select components of the endoplasmic reticulum stress response pathway. J Biochem Mol Toxicol. 2010 Mar-Apr;24(2):73-88.
• [13] 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.