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

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

doi:10.1016/j.bmcl.2004.02.101

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

Bioorg Med Chem Lett. 2004 May 17;14(10):2613-6. doi: 10.1016/j.bmcl.2004.02.101.

Authors

David W Borhani¹, David J Calderwood, Michael M Friedman, Gavin C Hirst, Biqin Li, Adelaine K W Leung, Brad McRae, Sheldon Ratnofsky, Kurt Ritter, Wendy Waegell

Affiliation

¹ Abbott Bioresearch Center, 100 Research Drive, Worcester, MA 01605-5314, USA.

PMID: 15109663
DOI: 10.1016/j.bmcl.2004.02.101

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.

MeSH terms

Administration, Oral
Animals
Dogs
Graft Rejection / drug therapy*
Heart Transplantation / adverse effects
Humans
Hypersensitivity, Delayed / drug therapy
Immunosuppressive Agents / chemical synthesis*
Immunosuppressive Agents / pharmacokinetics
Immunosuppressive Agents / 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
Pyrazoles / pharmacokinetics
Pyrazoles / therapeutic use*
Pyrimidines / administration & dosage
Pyrimidines / pharmacokinetics
Pyrimidines / therapeutic use*
Structure-Activity Relationship

Substances

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