The next generation of PDE4 inhibitors

被引：107

作者：

Huang, Z ^{[1
]}

Ducharme, Y ^{[1
]}

Macdonald, D ^{[1
]}

Robichaud, A ^{[1
]}

机构：

[1] Merck Frosst Ctr Therapeut Res, Pointe Claire, PQ H9R 4P8, Canada

来源：

CURRENT OPINION IN CHEMICAL BIOLOGY | 2001年 / 5卷 / 04期

关键词：

D O I：

10.1016/S1367-5931(00)00224-6

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A number of highly potent PDE4 inhibitors are being developed for the treatment of asthma, chronic obstructive pulmonary disease, rheumatoid arthritis, multiple sclerosis and Crohn's disease. Cilomilast (Ariflo(TM), SB 207499, SmithKline Beecham), the most advanced member of the class in Phase III clinical trials, was reported to have a limited therapeutic window. Other inhibitors with improved profiles in preclinical models are entering into (or are in) clinical trials. The recent developments in understanding PDE4 catalysis, inhibitor binding and their emetic response should facilitate the design of the next generation of PDE4 inhibitors.

引用

页码：432 / 438

页数：7

共 97 条

[1]

ALVAREZ R, 1995, MOL PHARMACOL, V48, P616

[2]

AMSCHLER H, 1995, Patent No. 9501338

[3]

Aoki M, 2000, J PHARMACOL EXP THER, V295, P1149

[4]

Aoki M, 2000, J PHARMACOL EXP THER, V295, P255

[5] Effect of PDE4 inhibitors on zymosan-induced IL-8 release from human neutrophils: Synergism with prostanoids and salbutamol [J].

Au, BT ;

Teixeira, MM ;

Collins, PD ;

Williams, TJ .

BRITISH JOURNAL OF PHARMACOLOGY, 1998, 123 (06) :1260-1266

[6] Sub-family selective actions in the ability of Erk2 MAP kinase to phosphorylate and regulate the activity of PDE4 cyclic AMP-specific phosphodiesterases [J].

Baillie, GS ;

MacKenzie, SJ ;

McPhee, I ;

Houslay, MD .

BRITISH JOURNAL OF PHARMACOLOGY, 2000, 131 (04) :811-819

[7]

Barnard A, 2000, J ROY ANTHROPOL INST, V6, P164

[8]

Barnette M S, 1999, Prog Drug Res, V53, P193

[9]

Barnette MS, 1996, BIOCHEM PHARMACOL, V51, P949

[10] UCR1 and UCR2 domains unique to the cAMP-specific phosphodiesterase family form a discrete module via electrostatic interactions [J].

Beard, MB ;

Olsen, AE ;

Jones, RE ;

Erdogan, S ;

Houslay, MD ;

Bolger, GB .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (14) :10349-10358

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