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Cyclic natriuretic peptide constructs

A technology of natriuretic peptides and constructs, applied in the direction of cyclic peptide components and the like

Inactive Publication Date: 2009-08-12
PALATIN TECH INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although effective, the pharmacokinetics and half-life of nestiritide are such that the product can only be used by intravenous infusion, limiting the use of this drug to hospital or experienced medical center settings
[0014] Despite the large number of compounds that have been developed, almost none have been commercialized or are in active clinical development

Method used

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  • Cyclic natriuretic peptide constructs
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  • Cyclic natriuretic peptide constructs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0535] The following constructs were synthesized, purified and quality determined using one or more of the amino acid substitutions described above, and the results are shown below:

[0536] Table 1

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Embodiment 2

[0572] The following constructs of Table 2 were synthesized, purified and quality determined using amino acid substitutions from one or more of the preceding methods:

[0573] Table 2

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Embodiment 3

[0579] Construct 1-1 with the following structure was tested as described above.

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[0581] In receptor binding studies, the average Ki of this construct in the assay system was 0.3 nM, with a Ki of 0.05 nM for hANP and a Ki of 0.6 nM for mini-ANP. EC of construct 1-1 in the assay system 50 2nM, where the EC of hANP 50 EC of 0.6nM, mini-ANP 50 is 3.3nM.

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Abstract

Cyclic constructs with an N-terminus and a C-terminus which bind to a natriuretic peptide receptor and include a plurality of amino acid residues, at least one amino acid surrogate of formula I: where R, R', Q, Y, W, Z, J, x and n are as defined in the specification, and optionally at least one prosthetic group, pharmaceutical compositions including such cyclic constructs, and methods of treatingcongestive heart failure or other conditions, syndromes or diseases for which induction of anti hypertensive, cardiovascular, renal or endocrine effects are desired.

Description

[0001] Cross References to Related Applications [0002] This application claims U.S. Provisional Patent Application Serial No. 60 / 743,960, filed March 30, 2006, entitled "Cyclic Natriuretic Peptide Constructs," and the filing March 30, 2006, entitled "Cyclic Natriuretic Peptide Constructs 60 / 743,961, and the specification and claims of each of said patent documents are hereby incorporated by reference. [0003] A related application entitled "Amino Acid Substitutes for Peptide Constructs" is hereby filed concurrently with International Patent Application PCT / US07 / 65632, Attorney Docket No. 0307-043-PCT, and the specification and claims of which are incorporated by reference way incorporated into this article. Background of the invention [0004] Field of invention (technical field): [0005] The present invention relates to a cyclic natriuretic peptide construct comprising a plurality of amino acid residues, one or more ring-constrained amino acid substitutes and optionally...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/12
Inventor S·D·沙拉马M·巴斯托斯杨炜蔡慧芝
Owner PALATIN TECH INC
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