Ontology highlight
ABSTRACT:
SUBMITTER: Huai Q
PROVIDER: S-EPMC2527038 | biostudies-literature | 2006 Mar
REPOSITORIES: biostudies-literature
Huai Qing Q Sun Yingjie Y Wang Huanchen H Macdonald Dwight D Aspiotis Renée R Robinson Howard H Huang Zheng Z Ke Hengming H
Journal of medicinal chemistry 20060301 6
Type 4 phosphodiesterase (PDE4) inhibitors are emerging as new treatments for a number of disorders including asthma and chronic obstructive pulmonary disease. Here we report the biochemical characterization on the second generation inhibitor (+)-1 (L-, IC50=0.4 nM) and its enantiomer (-)-1 (L-, IC50=43 nM) and their cocrystal structures with PDE4D at 2.0 A resolution. Despite the 107-fold affinity difference, both enantiomers interact with the same sets of residues in the rigid active site. The ...[more]