Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQKE41R)

• DOT Name: Lactadherin (MFGE8)
• Synonyms: Breast epithelial antigen BA46; HMFG; MFGM; Milk fat globule-EGF factor 8; MFG-E8; SED1
• Gene Name: MFGE8
• UniProt ID: MFGM_HUMAN
• Pfam ID: PF00008 ; PF00754
• Sequence:
  MPRPRLLAALCGALLCAPSLLVALDICSKNPCHNGGLCEEISQEVRGDVFPSYTCTCLKG
  YAGNHCETKCVEPLGLENGNIANSQIAASSVRVTFLGLQHWVPELARLNRAGMVNAWTPS
  SNDDNPWIQVNLLRRMWVTGVVTQGASRLASHEYLKAFKVAYSLNGHEFDFIHDVNKKHK
  EFVGNWNKNAVHVNLFETPVEAQYVRLYPTSCHTACTLRFELLGCELNGCANPLGLKNNS
  IPDKQITASSSYKTWGLHLFSWNPSYARLDKQGNFNAWVAGSYGNDQWLQVDLGSSKEVT
  GIITQGARNFGSVQFVASYKVAYSNDSANWTEYQDPRTGSSKIFPGNWDNHSHKKNLFET
  PILARYVRILPVAWHNRIALRLELLGC
• Function: Plays an important role in the maintenance of intestinal epithelial homeostasis and the promotion of mucosal healing. Promotes VEGF-dependent neovascularization. Contributes to phagocytic removal of apoptotic cells in many tissues. Specific ligand for the alpha-v/beta-3 and alpha-v/beta-5 receptors. Also binds to phosphatidylserine-enriched cell surfaces in a receptor-independent manner. Zona pellucida-binding protein which may play a role in gamete interaction; [Medin]: Main constituent of aortic medial amyloid.
• Tissue Specificity: Mammary epithelial cell surfaces and aortic media. Overexpressed in several carcinomas.
• KEGG Pathway: Efferocytosis (hsa04148)
• Reactome Pathway:
  Post-translational protein phosphorylation (R-HSA-8957275)
  Amyloid fiber formation (R-HSA-977225)
  Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) (R-HSA-381426)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Lactadherin (MFGE8) decreases the response to substance of Cisplatin.	[22]
Methotrexate	DM2TEOL	Approved	Lactadherin (MFGE8) affects the response to substance of Methotrexate.	[23]

23 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 Lactadherin (MFGE8).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Lactadherin (MFGE8).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Lactadherin (MFGE8).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Lactadherin (MFGE8).	[4]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Lactadherin (MFGE8).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Lactadherin (MFGE8).	[6]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Lactadherin (MFGE8).	[7]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Lactadherin (MFGE8).	[8]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Lactadherin (MFGE8).	[7]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Lactadherin (MFGE8).	[9]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of Lactadherin (MFGE8).	[10]
Menthol	DMG2KW7	Approved	Menthol increases the expression of Lactadherin (MFGE8).	[11]
Methyl aminolevulinate	DMIUX3D	Approved	Methyl aminolevulinate increases the expression of Lactadherin (MFGE8).	[12]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Lactadherin (MFGE8).	[13]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of Lactadherin (MFGE8).	[15]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Lactadherin (MFGE8).	[9]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Lactadherin (MFGE8).	[16]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Lactadherin (MFGE8).	[18]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Lactadherin (MFGE8).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Lactadherin (MFGE8).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Lactadherin (MFGE8).	[1]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Lactadherin (MFGE8).	[20]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Lactadherin (MFGE8).	[21]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Resveratrol	DM3RWXL	Phase 3	Resveratrol affects the response to substance of Lactadherin (MFGE8).	[14]

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 Lactadherin (MFGE8).	[17]

References

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• [4] Gamma-irradiation and doxorubicin treatment of normal human cells cause cell cycle arrest via different pathways. Mol Cells. 2005 Dec 31;20(3):331-8.
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• [6] 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.
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• [11] Repurposing L-menthol for systems medicine and cancer therapeutics? L-menthol induces apoptosis through caspase 10 and by suppressing HSP90. OMICS. 2016 Jan;20(1):53-64.
• [12] Efficacy of a methyl ester of 5-aminolevulinic acid in photodynamic therapy for ovarian cancers. J Cancer Res Clin Oncol. 2010 Aug;136(8):1143-50. doi: 10.1007/s00432-010-0761-7. Epub 2010 Jan 13.
• [13] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [14] Induction of lactadherin mediates the apoptosis of endothelial cells in response to advanced glycation end products and protective effects of grape seed procyanidin B2 and resveratrol. Apoptosis. 2011 Jul;16(7):732-45. doi: 10.1007/s10495-011-0602-4.
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• [17] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
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