publications

A novel JAK3 inhibitor, R348, attenuates chronic airway allograft rejection

Velotta JB, Deuse T, Haddad M, Masuda E, Park G, Carroll D, Taylor V, Robbins RC, Schrepfer S.

Transplantation. 2009 Mar 15;87(5):653-9.

BACKGROUND: This study aimed at investigating the role of a novel JAK3 inhibitor, R348, in the prevention of chronic airway allograft rejection. METHODS: The heterotopic rat trachea transplant model was used. Recipients were treated daily with R348 (10, 20, 40, 80 mg/kg) or rapamycin (0.75 or 3 mg/kg). Blood levels of R348 and of its active metabolite R333 were measured. Grafts were harvested after 28 days to analyze epithelial morphology, mononuclear infiltration, and luminal obliteration. Plasma levels of circulating donor strain-reactive IgG antibodies were quantified. CONCLUSIONS: R348 is an effective drug, and it is expected to be introduced into clinical transplant pharmacology soon.