Details of Drug Off-Target (DOT)

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

• DOT Name: Macrophage migration inhibitory factor (MIF)
• Synonyms: MIF; EC 5.3.2.1; Glycosylation-inhibiting factor; GIF; L-dopachrome isomerase; L-dopachrome tautomerase; EC 5.3.3.12; Phenylpyruvate tautomerase
• Gene Name: MIF
• UniProt ID: MIF_HUMAN
• PDB ID: 1CA7 ; 1CGQ ; 1GCZ ; 1GD0 ; 1GIF ; 1LJT ; 1MIF ; 1P1G ; 2OOH ; 2OOW ; 2OOZ ; 3B9S ; 3CE4 ; 3DJH ; 3DJI ; 3HOF ; 3IJG ; 3IJJ ; 3JSF ; 3JSG ; 3JTU ; 3L5P ; 3L5R ; 3L5S ; 3L5T ; 3L5U ; 3L5V ; 3SMB ; 3SMC ; 3U18 ; 3WNR ; 3WNS ; 3WNT ; 4ETG ; 4EUI ; 4EVG ; 4F2K ; 4GRN ; 4GRO ; 4GRP ; 4GRQ ; 4GRR ; 4GRU ; 4GUM ; 4K9G ; 4OSF ; 4OYQ ; 4P01 ; 4P0H ; 4PKK ; 4PKZ ; 4PLU ; 4TRF ; 4TRU ; 4WR8 ; 4WRB ; 4XX7 ; 4XX8 ; 4Z15 ; 4Z1T ; 4Z1U ; 5B4O ; 5BS9 ; 5BSC ; 5BSI ; 5BSJ ; 5EIZ ; 5HVS ; 5HVT ; 5HVV ; 5J7P ; 5J7Q ; 5UMJ ; 5UMK ; 5UZY ; 5V70 ; 5V73 ; 5XEJ ; 6B1C ; 6B1K ; 6B2C ; 6BG6 ; 6BG7 ; 6CB5 ; 6CBF ; 6CBG ; 6CBH ; 6FVE ; 6FVH ; 6OY8 ; 6OYB ; 6OYE ; 6OYG ; 6PEG ; 7E45 ; 7E47 ; 7E49 ; 7E4A ; 7E4B ; 7E4C ; 7KQX ; 7XTX ; 7XVX
• EC Number: 5.3.2.1; 5.3.3.12
• Pfam ID: PF01187
• Sequence:
  MPMFIVNTNVPRASVPDGFLSELTQQLAQATGKPPQYIAVHVVPDQLMAFGGSSEPCALC
  SLHSIGKIGGAQNRSYSKLLCGLLAERLRISPDRVYINYYDMNAANVGWNNSTFA
• Function: Pro-inflammatory cytokine involved in the innate immune response to bacterial pathogens. The expression of MIF at sites of inflammation suggests a role as mediator in regulating the function of macrophages in host defense. Counteracts the anti-inflammatory activity of glucocorticoids. Has phenylpyruvate tautomerase and dopachrome tautomerase activity (in vitro), but the physiological substrate is not known. It is not clear whether the tautomerase activity has any physiological relevance, and whether it is important for cytokine activity.
• KEGG Pathway:
  Tyrosine metabolism (hsa00350)
  Phenylalanine metabolism (hsa00360)
  Metabolic pathways (hsa01100)
• Reactome Pathway:
  Neutrophil degranulation (R-HSA-6798695)
  Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation (R-HSA-8950505)
  Cell surface interactions at the vascular wall (R-HSA-202733)

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
Amphotericin B	DMTAJQE	Approved	Macrophage migration inhibitory factor (MIF) increases the Cell death ADR of Amphotericin B.	[24]
Ardeparin	DMYRX8B	Approved	Macrophage migration inhibitory factor (MIF) affects the binding of Ardeparin.	[25]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Macrophage migration inhibitory factor (MIF).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Macrophage migration inhibitory factor (MIF).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Macrophage migration inhibitory factor (MIF).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Macrophage migration inhibitory factor (MIF).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Macrophage migration inhibitory factor (MIF).	[5]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Macrophage migration inhibitory factor (MIF).	[6]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Macrophage migration inhibitory factor (MIF).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Macrophage migration inhibitory factor (MIF).	[8]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Macrophage migration inhibitory factor (MIF).	[9]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Macrophage migration inhibitory factor (MIF).	[1]
Folic acid	DMEMBJC	Approved	Folic acid affects the expression of Macrophage migration inhibitory factor (MIF).	[11]
Benzatropine	DMF7EXL	Approved	Benzatropine increases the expression of Macrophage migration inhibitory factor (MIF).	[12]
Tanespimycin	DMNLQHK	Phase 2	Tanespimycin decreases the expression of Macrophage migration inhibitory factor (MIF).	[13]
PMID26560530-Compound-35	DMO36RL	Patented	PMID26560530-Compound-35 increases the expression of Macrophage migration inhibitory factor (MIF).	[16]
Clioquinol	DM746BZ	Withdrawn from market	Clioquinol increases the expression of Macrophage migration inhibitory factor (MIF).	[17]
SB-431542	DM0YOXQ	Preclinical	SB-431542 increases the expression of Macrophage migration inhibitory factor (MIF).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Macrophage migration inhibitory factor (MIF).	[19]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Macrophage migration inhibitory factor (MIF).	[20]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Macrophage migration inhibitory factor (MIF).	[22]
Rutin	DMEHRAJ	Investigative	Rutin increases the expression of Macrophage migration inhibitory factor (MIF).	[23]
CATECHIN	DMY38SB	Investigative	CATECHIN decreases the expression of Macrophage migration inhibitory factor (MIF).	[23]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the secretion of Macrophage migration inhibitory factor (MIF).	[10]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the secretion of Macrophage migration inhibitory factor (MIF).	[21]

2 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 increases the methylation of Macrophage migration inhibitory factor (MIF).	[14]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Macrophage migration inhibitory factor (MIF).	[15]

References

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• [9] Proteomic and functional analyses reveal a dual molecular mechanism underlying arsenic-induced apoptosis in human multiple myeloma cells. J Proteome Res. 2009 Jun;8(6):3006-19.
• [10] Chronic senescent human mesenchymal stem cells as possible contributor to the wound healing disorder after exposure to the alkylating agent sulfur mustard. Arch Toxicol. 2021 Feb;95(2):727-747. doi: 10.1007/s00204-020-02946-5. Epub 2021 Jan 25.
• [11] Folate deficiency in normal human fibroblasts leads to altered expression of genes primarily linked to cell signaling, the cytoskeleton and extracellular matrix. J Nutr Biochem. 2007 Aug;18(8):541-52. doi: 10.1016/j.jnutbio.2006.11.002. Epub 2007 Feb 22.
• [12] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [13] Impact of Heat Shock Protein 90 Inhibition on the Proteomic Profile of Lung Adenocarcinoma as Measured by Two-Dimensional Electrophoresis Coupled with Mass Spectrometry. Cells. 2019 Jul 31;8(8):806. doi: 10.3390/cells8080806.
• [14] 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.
• [15] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [16] Rottlerin impairs early and late steps of Toxoplasma gondii infection in human trophoblast cells and villous explants. Chem Biol Interact. 2023 Oct 1;384:110716. doi: 10.1016/j.cbi.2023.110716. Epub 2023 Sep 16.
• [17] Identification of chemical compounds that induce HIF-1alpha activity. Toxicol Sci. 2009 Nov;112(1):153-63.
• [18] Activin/nodal signaling switches the terminal fate of human embryonic stem cell-derived trophoblasts. J Biol Chem. 2015 Apr 3;290(14):8834-48.
• [19] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
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• [21] Formaldehyde Gas Exposure Increases Inflammation in an In Vitro Model of Dry Eye. Toxicol Sci. 2018 Sep 1;165(1):108-117. doi: 10.1093/toxsci/kfy125.
• [22] Molecular targets of chloropicrin in human airway epithelial cells. Toxicol In Vitro. 2017 Aug;42:247-254.
• [23] Epicatechin and a cocoa polyphenolic extract modulate gene expression in human Caco-2 cells. J Nutr. 2004 Oct;134(10):2509-16.
• [24] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [25] Cell surface syndecan-1 contributes to binding and function of macrophage migration inhibitory factor (MIF) on epithelial tumor cells. Biochim Biophys Acta. 2016 Apr;1863(4):717-26. doi: 10.1016/j.bbamcr.2016.02.003. Epub 2016 Feb 4.