Discovery of A-770041, a src-family selective orally active lck inhibitor that prevents organ allograft rejection

We describe the identification, SAR, and pharmacology of the src-family selective lck inhibitor A-770041 that prolongs the survival of major histocompatibility mismatched allografts in models of solid organ transplant rejection for greater than 65 days. We describe the identification, SAR, and pharm...

Full description

Saved in:
Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2006-01, Vol.16 (1), p.118-122
Main Authors: Burchat, Andrew, Borhani, David W., Calderwood, David J., Hirst, Gavin C., Li, Biqin, Stachlewitz, Robert F.
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Chemistry, Pharmaceutical - methods
Crystallography, X-Ray
Drug Design
Enzyme Inhibitors - pharmacology
Graft Rejection - prevention & control
Heart Transplantation - methods
Humans
Immunomodulators
Immunophenotyping
Immunosuppressive Agents - pharmacology
Inhibitory Concentration 50
Kinase inhibitor
Kinetics
Lck inhibitor
Lymphocyte Specific Protein Tyrosine Kinase p56(lck) - antagonists & inhibitors
Major Histocompatibility Complex
Medical sciences
Models, Chemical
Models, Molecular
Pharmaceutical Preparations
Pharmacology. Drug treatments
Pyrazoles - chemical synthesis
Pyrazoles - pharmacology
Pyrimidines - chemical synthesis
Pyrimidines - pharmacology
Rats
Src-family
src-Family Kinases - antagonists & inhibitors
Time Factors
Transplant rejection
Transplantation, Homologous - methods
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:We describe the identification, SAR, and pharmacology of the src-family selective lck inhibitor A-770041 that prolongs the survival of major histocompatibility mismatched allografts in models of solid organ transplant rejection for greater than 65 days. We describe the identification, SAR, and pharmacology of the src-family selective lck inhibitor A-770041 that prolongs the survival of major histocompatibility mismatched allografts in models of solid organ transplant rejection for greater than 65 days.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2005.09.039