Method for the treatment of polycystic kidney disease

A polycystic kidney disease, disease technology, applied in the direction of urinary system diseases, pharmaceutical formulations, organic active ingredients, etc., can solve the problems of polycystic kidney disease treatment and other problems

Inactive Publication Date: 2008-01-09
WYETH LLC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] However, there is currently no fully effective treatment for polycystic kidney disease

Method used

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  • Method for the treatment of polycystic kidney disease
  • Method for the treatment of polycystic kidney disease
  • Method for the treatment of polycystic kidney disease

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0163] In vitro against primitive collecting tubule (CT) cells from human polycystic kidney disease (PKD) samples, control and cystic primitive CT cells from rat analogs of human PKD, and BPK mice from PKD Model control and cystic conditional immortalized CT cells TACE inhibitor alone or in combination with Src inhibitor, HER-2 inhibitor or combination Src inhibitor and HER-2 inhibitor or Src inhibitor and HER-2 inhibitor Combinations of combinations are studied. Shows signs of cyst development and reduced growth. Additional information on compound toxicity, cell proliferation, site-specific phosphorylation levels of EGFR, c-Src, MEK, and downstream targets is also presented.

example 2

[0165] In vivo studies of TACE inhibitors alone or in combination with Src inhibitors, HER-2 inhibitors, or combinations of Src inhibitors and HER-2, or Src inhibitors and HER- 2 Combinations of Inhibitors Combinations of inhibitors were studied to determine the efficacy of the compounds alone or in combination to ameliorate both renal and hepatic cyst development and growth progression. A pilot study was performed on 3 control rats and 3 cystic rats using doses between 10 and 60 mg / kg every day and every three days. From day 7 after birth, Src inhibitors were administered intraperitoneally at different concentrations and frequencies until day 28 after birth. Surviving kidney and liver function, morphological analysis (cyst size and number), and site-specific phosphorylation levels of c-Src upstream and downstream targets were assessed. 10 control animals and 10 cystic animals were treated for a minimum of 10 weeks when determining the dose with maximal effect and least toxic...

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Abstract

The present invention provides a method for treating, inhibiting the progression of, or eradicating polycystic kidney disease of in a patient in need thereof which comprises providing to said patient an effective amount of a TACE inhibitor compound alone or in combination with an effective amount of a Src kinase inhibitor, a HER-2 kinase inhibitor, or a combination of Src and HER-2 inhibitor.

Description

technical field [0001] The invention relates to a method for treating polycystic kidney disease. More specifically, it relates to the treatment of disease using tumor necrosis factor-alpha converting enzyme (TACE) inhibitors in combination with other agents such as Src and human epidermal growth factor receptor-2 (HER-2) kinase inhibitors. Background technique [0002] Autosomal recessive polycystic kidney disease (ARPKD) is an inherited disorder with severe renal enlargement (due to rapid cyst expansion) and hepatic fibrosis, usually in the neonatal period. ARPKD occurs in approximately 1:10,000 to 1:40,000 births and causes significant morbidity and mortality. Data from experimental models of both recessive and overt forms of PKD have demonstrated three key pathophysiological processes in cyst formation and enlargement: increased cellular proliferation, increased fluid secretion, and altered stromal biology. (Marcia NS, Sweeny WE Armer ED: New insights into the molecular...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/18A61K31/47A61K31/54A61K31/5513A61K45/06A61P35/00
CPCA61K31/47A61K31/5513A61K31/18A61K45/06A61K31/54A61P13/00A61P13/12A61P35/00A61K2300/00
Inventor 菲利普·弗罗斯特
Owner WYETH LLC
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