ISOFORM-SELECTIVE INHIBITOR AND ACTIVATORS OF PDE3 CYCLIC NUCLEOTIDE PHOSPHODIESTERASES
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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.
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Citations
23 Claims
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1. (canceled)
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9-20. -20. (canceled)
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21. A method of identifying an isoform-selective regulator of PDE3, said method comprising:
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(a) obtaining an isolated polypeptide, wherein the polypeptide has an amino acid sequence that is at least 95% homologous to the amino acid sequence of SEQ ID NO;
1;(b) identifying at least one test compound that binds to the isolated a first polypeptide; (c) assaying the at least one test compound for its ability to interfere with binding of the first polypeptide to PDE3 cAMP or cGMP; (d) assaying the at least one test compound for its ability to interfere with binding of a second polypeptide to cAMP or cGMP; and (e) wherein a test compound with the binding interference of the first polypeptide is greater than the binding interference to the second polypeptide is an isoform-selective regulator of PDE3. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 22)
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23-26. -26. (canceled)
Specification