Macrophage migration inhibitory factor and the discovery of tautomerase inhibitors.

Abstract:

:Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine released from T-cells and macrophages, and is a key molecule in inflammation. Although a detailed understanding of the biological functions of MIF has not yet been found, it is known that MIF catalyzes the tautomerization of phenylpyruvate and a non-physiological molecule, D-dopachrome. A potent tautomerase inhibitor would be expected, as a validation tool, to shed light on role of MIF activity and the relationship between its biological and enzymatic activity. Such tautomerase inhibitors would be useful in the treatment of MIF-related diseases, such as sepsis, acute respiratory distress syndrome (ARDS), asthma, atopic dermatitis, rheumatoid arthritis (RA), nephropathy and tumors. In this review, we have focused on (1) the biological and enzymatic activities of MIF, (2) the discovery of novel, drug-like tautomerase inhibitors of MIF using a structure-based computer-assisted search, and (3) a crystallographic and molecular modeling study of the MIF-tautomerase inhibitor complexes (A review with 133 references).

journal_name

Curr Pharm Des

authors

Orita M,Yamamoto S,Katayama N,Fujita S

doi

10.2174/1381612023394674

subject

Has Abstract

pub_date

2002-01-01 00:00:00

pages

1297-317

issue

14

eissn

1381-6128

issn

1873-4286

journal_volume

8

pub_type

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