A-420983: a potent, orally active inhibitor of lck with efficacy in a model of transplant rejection.
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.
Borhani
David W
DW
Abbott Bioresearch Center, 100 Research Drive, Worcester, MA 01605-5314, USA.
Calderwood
David J
DJ
Friedman
Michael M
MM
Hirst
Gavin C
GC
Li
Biqin
B
Leung
Adelaine K W
AK
McRae
Brad
B
Ratnofsky
Sheldon
S
Ritter
Kurt
K
Waegell
Wendy
W
D000284:Administration, Oral; D000818:Animals; D004285:Dogs; D006084:Graft Rejection / Q000188:drug therapy*; D016027:Heart Transplantation / Q000009:adverse effects; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000188:drug therapy; D007166:Immunosuppressive Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000627:therapeutic use; D020128:Inhibitory Concentration 50; D007376:Interleukin-2 / Q000096:biosynthesis; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000037:antagonists & inhibitors*; D051379:Mice; D008810:Mice, Inbred C57BL; D008862:Microsomes, Liver; D023421:Models, Animal; D008958:Models, Molecular; D015394:Molecular Structure; D011720:Pyrazoles / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011743:Pyrimidines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013329:Structure-Activity Relationship
D007166:Immunosuppressive Agents; D007376:Interleukin-2; D011720:Pyrazoles; D011743:Pyrimidines; C014175:pyrazolo(3,4-d)pyrimidine; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)