Methods relating to the treatment of fibrosis

a fibrosis and fibrosis technology, applied in the field of fibrosis treatment, can solve the problems of ipf death greatly underreported, inability to recognize ipf considerable morbidity, progressive scarring and lung destruction,

Inactive Publication Date: 2008-06-26
UNIV OF WASHINGTON +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0023]The compound V (ICG-001) is useful for treating fibrosis as described in Example 1.
[0024]These and other aspects of this invention will be apparent upon reference to the attached figures and followin...

Problems solved by technology

It is believed that death due to IPF is greatly underreported and the considerable morbidity of IPF is not recognized.
Pulmonary fibrosis leads to progressive scarring and lung destruction.
The fibrosis is refractory to corticosteroids and no effective therapy currently exists.
While advances in molecular biology and computational chemistry have led to increased interest in what has been termed “rational drug design”, such techniques have not proven as fast or reliable as initially predicted.
Initially, ...

Method used

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  • Methods relating to the treatment of fibrosis
  • Methods relating to the treatment of fibrosis
  • Methods relating to the treatment of fibrosis

Examples

Experimental program
Comparison scheme
Effect test

example 1

Effect of ICG-001 on Pulmonary Fibrosis

[0083]Murine models of bleomycin induced fibrosis have been developed in order to study fibrotic disease progression. Bleomycin induced murine fibrosis has been shown to lead to aberrant alveolar epithelial repair, with increased metaplastic alveolar cells that apparently do not properly differentiate to a type I phenotype (Adamson and Bowden 1979 Am J Pathol. 1979 August; 96(2):531-44.). Utilizing this model it is demonstrated in this Example that the Wnt / β-catenin pathway plays a critical role in the development of pulmonary fibrosis and validates that the inhibition of this pathway with ICG-001 represents a therapy for the treatment of pulmonary fibrotic disease.

[0084]Using this murine model of pulmonary fibrosis in transgenic Bat-al mice, ICG-001 (5 mg / Kg / day) blocked >95% of bleomycin-induced TCF / βcatenin transcription. Furthermore, ICG-001 at this dose not only halted but reversed disease progression, as judged by reduced mortality, histo...

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Abstract

The invention provides α-helix mimetic structures of formula (I) with the definitions of A, B, D, E, G, W, R1 and R2 as set out in the description and a chemical library relating thereto. The compounds, pharmaceutical compositions comprising the compounds, and methods of the invention using the compounds, relate to the reversal of fibrotic conditions, such as pulmonary fibrosis.

Description

CROSS REFERENCE TO RELATED APPLICATION(S)[0001]The present application is a continuation of PCT International Patent Application No. PCT / US2006 / 009191, filed Mar. 15, 2006, which claims priority from U.S. Provisional Application No. 60 / 663,499, filed Mar. 18, 2005, both of which are hereby incorporated by reference in their entirety.STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT[0002]This invention was made with government support under grant R01 HL073722 awarded by the National Institutes of Health. The government has certain rights in the invention.[0003]The subject matter of this application was made with support from the United States Government under The National Institutes of Health, Grant No. R01 HL073722. The U.S. Government may have certain rights.TECHNICAL FIELD[0004]The present invention relates generally to α-helix mimetic structures and to a chemical library relating thereto. The invention also relates to applications in the treatment of diseases and ph...

Claims

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Application Information

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IPC IPC(8): A61K38/12A61P3/00A61P11/00A61P19/00A61P17/00
CPCC07K7/56A61P1/16A61P11/00A61P13/12A61P15/00A61P17/00A61P19/00A61P25/28A61P27/02A61P27/06A61P29/00A61P3/00A61P43/00A61P7/04C07D487/04A61K31/4985
Inventor HENDERSON, WILLIAM R.CHI, EMIL Y.KAHN, MICHAEL
Owner UNIV OF WASHINGTON
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