Macrophage Migration Inhibitory Factor and the Discovery of Tautomerase Inhibitors
Authors: Orita, M.; Yamamoto, S.; Katayama, N.; Fujita, S.
Source: Current Pharmaceutical Design, Volume 8, Number 14, 1 June 2002 , pp. 1297-1317(21)
Publisher: Bentham Science Publishers
Key:
- Free Content
- New Content
- Subscribed Content
- Free Trial Content
- Free Content
- New Content
- Subscribed Content
- Free Trial Content
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 nonphysiological 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).Keywords: mif; tautomerase inhibitor; doachrome
Document Type: Review article
DOI: 10.2174/1381612023394674
Key:
- Free Content
- New Content
- Subscribed Content
- Free Trial Content
- Free Content
- New Content
- Subscribed Content
- Free Trial Content
Click here for Page Help