Publikation

The specific monocarboxylate transporter (MCT1) inhibitor, AR-C117977, a novel immunosuppressant, prolongs allograft survival in the mouse

Wissenschaftlicher Artikel/Review - 15.11.2007

Bereiche
PubMed
DOI

Zitation
Bueno V, Binet F, Steger U, Bundick R, Ferguson D, Murray C, Donald D, Wood K. The specific monocarboxylate transporter (MCT1) inhibitor, AR-C117977, a novel immunosuppressant, prolongs allograft survival in the mouse. Transplantation 2007; 84:1204-7.
Art
Wissenschaftlicher Artikel/Review (Englisch)
Zeitschrift
Transplantation 2007; 84
Veröffentlichungsdatum
15.11.2007
ISSN (Druck)
0041-1337
Seiten
1204-7
Kurzbeschreibung/Zielsetzung

Novel small molecular weight compounds that act by inhibiting the monocarboxylate transporter (MCT1) receptor have been found to cause profound inhibition of T-cell responses to alloantigen in vitro. Here, we have investigated the ability of one compound in this series, AR-C117977, a potent MCT1 inhibitor, to prevent the acute and chronic rejection of vascularized and nonvascularized allografts in the mouse. Treatment with AR-C117977 or cyclosporin A (CsA) administered at a dose of 30 mg/kg subcutaneously for 15 days to adult CBA. Ca (H2(k)) mice, commencing either 3 days or 1 day before transplantation, was found to prolong the survival of an allogeneic (C57BL/10 H2(b); NZW H2(z); or BALB/c H2(d)) heart, aorta, or skin allograft significantly compared with treatment with vehicle alone (median survival time [MST] AR-C117977 treated 15; 19 and 18 days [skin] and 73; 66 and 67 days ([heart] vs. vehicle treated 8, 8 and 9 days [skin] and 9, 8, 10 days [heart] for B10, NZW and BALB grafts, respectively). AR-C117977 also inhibited the development of transplant arteriosclerosis in aortic allografts partially, but was unable to inhibit alloantibody production after transplantation. The specific MCT1 inhibitor AR-C117977 has potent immunosuppressive properties in vivo effectively preventing acute but not chronic allograft rejection in the mouse.