Isoform-selective inhibitors and activators of PDE3 cyclic nucleotide phosphodiesterases
OwnerMatthew A. Movsesianinventor
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Abstract
The present invention concerns methods and compositions related to type 3 phosphodiesterases (PDE3). Certain embodiments concern isolated peptides corresponding to various PDE3A isoforms and/or site-specific mutants of PDE3A isoforms, along with expression vectors encoding such isoforms or mutants. In specific embodiments, methods for identifying isoform selective inhibitors or activators of PDE3 are provided, along with methods of use of such inhibitors or activators in the treatment of dilated cardiomyopathy, pulmonary hypertension and/or other medical conditions related to PDE3 effects on cAMP levels in different intracellular compartments.
Claims26
An isolated polypeptide consisting of an amino acid sequence that is at least 95% homologous to SEQ ID NO:1, SEQ ID NO:2 or SEQ ID NO:3.
The expression vector comprising a nucleic acid encoding an isoform of type 3 phosphodiesterase.
A method of modulating cardiac contractility comprising administering to an individual a pharmacologically effective amount of an isoform selective inhibitor, activator or regulator of PDE3.
A method of treating an individual with dilated cardiomyopathy and/or pulmonary hypertension comprising administering to the individual a pharmacologically effective amount of an isoform selective inhibitor, activator or regulator of PDE3.
Dependencies are inferred from the claim text.