Use of Lck inhibitors for treatment of immunologic diseases

a technology of immunologic diseases and lck inhibitors, which is applied in the field of immunologic disease treatment or pathological conditions, can solve the problems of kidney failure in a substantial number of patients and unwanted side effects

Inactive Publication Date: 2009-12-10
BOEHRINGER INGELHEIM PHARMA KG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The leading agent for prevention or treatment of transplant rejection is cyclosporin A which, although effective, is often associated with side-effects such as renal damage and hypertension, which results in kidney failure in a substantial number of patients.
It is contemporary practice to treat rheumatoid arthritis initially with symptom relief agents such as NSAIDs, which have no effect on disease progression and are often associated with unwanted side-effects.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

example 1

Non-Radioactive Kinase Assay (Ick)

Methodology

[0089]The Ick enzyme comprises the entire Ick molecule except the first nine amino acids which are replaced by an His-tag for purification purposes. The enzyme is affinity purified.

[0090]The assay mix is assembled in a well of a 96-well round bottom microtiter plate and contains 10 μl PBS (either as such or with an inhibitor dissolved at an appropriate concentration), 20 μl substrate solution (200 mM Hepes, pH=7.4; 50 mM MgAc2; 1 mM Na3VO4; 250 pg / ml poly-Glu-Tyr (Sigma PO275); 200 ng / ml biotinylated peptide (biot-Ala-Glu-Glu-Glu-11e-Tyr-Gly-Glu-Phe-Glu-Ala-Lys-Lys-Lys-Lys) and 20 μl of 2.5 ng / μl enzyme (diluted from affinity purified stock with enzyme dilution buffer, EDB: 20 mM Hepes, pH=7.4, 130 mM NaCl, 0.05% Triton X-100).

[0091]The reaction is started by the addition of 50 μl 500 μM ATP (in 10 mM MgAc2) and is performed at room temperature. After 30 minutes 50 μl stop solution (20 mM Hepes, pH=7.4; 250 mM EDTA) are added and 100 μl o...

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Abstract

The invention relates to a method of treating immunologic diseases or pathological conditions involving an immunologic component using certain Lck inhibitors already known as kinase inhibitors for therapy in oncology, optionally in combination with one or more other drugs selected from NSAIDs, steroids, DMARDs, immunsuppressives, biologic response modifiers and antinfectives, pharmaceutical compositions comprising said Lck inhibitors together with said other drugs, and the use of the Lck inhibitors for the manufacture of a pharmaceutical composition for the treatment of immunologic diseases or pathological conditions involving an immunologic component.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application is a continuation of U.S. patent application Ser. No. 10 / 640,926, filed Aug. 14, 2003.TECHNICAL FIELD OF THE INVENTION[0002]This invention relates to a method for treating immunologic diseases or pathological conditions, which conditions have an immunologic component, using a compound selected from compounds (A) to (AL) listed below. Such compounds are already known as kinase inhibitors for therapy in oncology.BACKGROUND OF THE INVENTION[0003]Compounds (A) to (AL) listed below, their preparation as well as the pharmacological activity of these compounds based on inhibition of kinases, e.g., VEGFR-2, suitable for therapy in oncology, are disclosed in WO 02 / 36564, WO 99 / 52869, WO 00 / 18734, WO 00 / 73297, WO 01 / 27080, WO 01 / 27081 and WO 01 / 32651. The cited documents are herewith incorporated by reference.[0004]Lck, a further tyrosine kinase belonging to the src family of tyrosine kinases not mentioned in the references cited a...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/404A61K31/454A61K31/517A61P37/00A61P29/00A61K45/06
CPCA61K31/404A61K31/454A61K31/517A61K45/06A61K2300/00A61P29/00A61P37/00
Inventor ROTH, GERALD JUERGENHECKEL, ARMINWALTER, RAINERHILBERG, FRANKHAUPTMANN, RUDOLFSTEFANIC, MARTIN FREDRICHCOLBATZKY, FLORIANERNEST, STEFFAN
Owner BOEHRINGER INGELHEIM PHARMA KG
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