Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT2AST1)

• DTT Name: Macrophage migration inhibitory factor (MIF)
• Synonyms: Phenylpyruvate tautomerase; MMIF; L-dopachrome tautomerase; L-dopachrome isomerase; Glycosylation-inhibiting factor; GLIF; GIF
• Gene Name: MIF
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Intramolecular oxidoreductase
• UniProt ID: MIF_HUMAN
• TTD ID: T39977
• EC Number: EC 5.3.2.1
• Sequence:
  MPMFIVNTNVPRASVPDGFLSELTQQLAQATGKPPQYIAVHVVPDQLMAFGGSSEPCALC
  SLHSIGKIGGAQNRSYSKLLCGLLAERLRISPDRVYINYYDMNAANVGWNNSTFA
• Function: 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. Pro-inflammatory cytokine.
• KEGG Pathway:
  Tyrosine metabolism (hsa00350)
  Phenylalanine metabolism (hsa00360)
• 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 DTT

2 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
3,4-Dihydroxycinnamic Acid	DMVZL26	Thrombocytopenia	3B64	Phase 4	[2]
Anti-MIF antibodies	DM8EKSV	Autoimmune diabetes	5A10	Phase 4	[1]

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ISO-1	DMDB7KU	N. A.	N. A.	Phase 1	[3]

1 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
COR100140	DMN0GTR	Inflammation	1A00-CA43.1	Preclinical	[4]

6 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
4-HYDROXYBENZALDEHYDE O-(CYCLOHEXYLCARBONYL)OXIME	DM7WPGN	Discovery agent	N.A.	Investigative	[5]
4-hydroxyphenylpyruvic acid	DM0564K	Discovery agent	N.A.	Investigative	[5]
6-HYDROXY-1,3-BENZOTHIAZOLE-2-SULFONAMIDE	DMPSOIF	Discovery agent	N.A.	Investigative	[5]
AVP-13546	DMDTONZ	Autoimmune disease	4A40-4A45	Investigative	[6]
AVP-13748	DMBNDYK	Autoimmune disease	4A40-4A45	Investigative	[6]
NAPQI	DM8F5LR	Autoimmune disease	4A40-4A45	Investigative	[6]

References

• [1] Neutralization of Macrophage Migration Inhibitory Factor (MIF) by Fully Human Antibodies Correlates with Their Specificity for the beta-Sheet Structure of MIF. J Biol Chem. 2012 March 2; 287(10): 7446-7455.
• [2] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [3] The tautomerase active site of macrophage migration inhibitory factor is a potential target for discovery of novel anti-inflammatory agents. J Biol Chem. 2002 Jul 12;277(28):24976-82.
• [4] Cortical Pty Ltd Presents MIF Antagonist Data at World Congress on Inflammation. Cortical Pty Ltd. 2005.
• [5] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [6] MIF in autoimmunity and novel therapeutic approaches. Autoimmun Rev. 2009 Jan;8(3):244-9.