A-420983: a potent, orally active inhibitor of lck with efficacy in a model of transplant rejection.

Abstract

We have identified the pyrazolo[3,4-d]pyrimidine A-420983 (compound 7) as a potent inhibitor of lck. A-420983 exhibits oral efficacy in animal models of delayed-type hypersensitivity and organ transplant rejection.

• Authors: David W Borhani, David J Calderwood, Michael M Friedman, Gavin C Hirst, Biqin Li, Adelaine K W Leung, Brad McRae, Sheldon Ratnofsky, Kurt Ritter, Wendy Waegell
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 14 Issue 10 Pg. 2613-6 (May 17 2004) ISSN: 0960-894X [Print] England
• PMID: 15109663 (Publication Type: Journal Article)

Chemical References

• Immunosuppressive Agents
• Interleukin-2
• Pyrazoles
• Pyrimidines
• pyrazolo(3,4-d)pyrimidine
• Lymphocyte Specific Protein Tyrosine Kinase p56(lck)

Topics

• Administration, Oral
• Animals
• Dogs
• Graft Rejection (drug therapy)
• Heart Transplantation (adverse effects)
• Humans
• Hypersensitivity, Delayed (drug therapy)
• Immunosuppressive Agents (chemical synthesis, pharmacokinetics, therapeutic use)
• Inhibitory Concentration 50
• Interleukin-2 (biosynthesis)
• Lymphocyte Specific Protein Tyrosine Kinase p56(lck) (antagonists & inhibitors)
• Mice
• Mice, Inbred C57BL
• Microsomes, Liver
• Models, Animal
• Models, Molecular
• Molecular Structure
• Pyrazoles (administration & dosage, pharmacokinetics, therapeutic use)
• Pyrimidines (administration & dosage, pharmacokinetics, therapeutic use)
• Structure-Activity Relationship