MIF

Synonyms

Glycosylation-inhibiting factor, L-dopachrome isomerase, MIF, Macrophage Migration Inhibitory Factor, Macrophage Migration Inhibitory Factor (Glycosylation-Inhibiting Factor), GLIF, MMIF, EC:5.3.2.1, GIF, EC 5.3.3.12, EC 5.3.2.1, Macrophage Migration-Inhibitory Factors, Epididymis Secretory Sperm Binding Protein, EC:5.3.3.12, Phenylpyruvate Tautomerase, L-Dopachrome Tautomerase

Description

MIF is an important regulator of innate immunity.The MIF protein superfamily also includes a second member with functionally related properties, the D-dopachrome tautomerase (D-DT).CD74 is a surface receptor for MIF.Macrophage migration inhibitory factor is a protein that in humans is encoded by the MIF gene.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.

KO Status

Immunization

Drug Information

Launched drug: 1
Drug in clinical trials: 1
Latest Research Phase: Approved

Drug Name

Code

Phase

Company

Indications

Clinical Trials

Ibudilast

AV-411, KC-404, MN-166

Approved

Diabetic Neuropathies, Multiple Sclerosis, Chronic Progressive, Multiple Sclerosis, Pneumonia, Viral, Asthma, Neuralgia, Amyotrophic Lateral Sclerosis

Imalumab

BAX-69, BAX-069

Phase 2 Clinical

Cytokine Pharmasciences

Ovarian Neoplasms, Lupus Nephritis, Ascites, Colorectal Neoplasms

Melanoma vaccine (AlphaVax)

Preclinical

Alphavax

Melanoma

CPSI-2705

CPS1-2705

Pending

Cytokine Pharmasciences

Communicable Diseases

R-ISO-15

Pending

Ferring Bv

Sepsis

CBX-21404

CBX-21404

Pending

Ciblex

Autoimmune Diseases, Breast Neoplasms, Prostatic Neoplasms, Inflammation

References


Title

Authors

Source

Coumarin and chromen-4-one analogues as tautomerase inhibitors of macrophage migration inhibitory factor: discovery and X-ray crystallography

Orita M., Yamamoto S., Katayama N., Aoki M., Takayama K., Yamagiwa Y., Seki N., Suzuki H., Kurihara H., Sakashita H., Takeuchi M., Fujita S., Yamada T., Tanaka A.,

J. Med. Chem. 44:540-547(2001)

Alternative chemical modifications reverse the binding orientation of a pharmacophore scaffold in the active site of macrophage migration inhibitory factor

Crichlow G.V., Cheng K.F., Dabideen D., Ochani M., Aljabari B., Pavlov V.A., Miller E.J., Lolis E., Al-Abed Y.,

J. Biol. Chem. 282:23089-23095(2007)

Structural and kinetic analyses of macrophage migration inhibitory factor active site interactions

Crichlow G.V., Lubetsky J.B., Leng L., Bucala R., Lolis E.J.,

Biochemistry 48:132-139(2009)

MIF intersubunit disulfide mutant antagonist supports activation of CD74 by endogenous MIF trimer at physiologic concentrations

Fan C., Rajasekaran D., Syed M.A., Leng L., Loria J.P., Bhandari V., Bucala R., Lolis E.J.,

Proc. Natl. Acad. Sci. U.S.A. 110:10994-10999(2013)

A genome annotation-driven approach to cloning the human ORFeome

Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., Beare D.M., Dunham I.,

Genome Biol. 5:R84.1-R84.11(2004)

Complete sequencing and characterization of 21,243 full-length human cDNAs

Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., Sugano S.,

Nat. Genet. 36:40-45(2004)

The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)

The MGC Project Team,

Genome Res. 14:2121-2127(2004)

Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides

Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., Vandekerckhove J.,

Nat. Biotechnol. 21:566-569(2003)

Human liver protein map: a reference database established by microsequencing and gel comparison

Hochstrasser D.F., Frutiger S., Paquet N., Bairoch A., Ravier F., Pasquali C., Sanchez J.-C., Tissot J.-D., Bjellqvist B., Vargas R., Appel R.D., Hughes G.J.,

Electrophoresis 13:992-1001(1992)

The major binding protein of the interferon antagonist sarcolectin in human placenta is a macrophage migration inhibitory factor

Zeng F.Y., Weiser W.Y., Kratzin H., Stahl B., Karas M., Gabius H.J.,

Arch. Biochem. Biophys. 303:74-80(1993)