Clare M. Murray

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BACKGROUND In a search for immunosuppressive drugs having novel mechanisms, monocarboxylate transporter (MCT-1) inhibitors were identified that markedly inhibited immune responses. Here, we report the effects of AR-C117977, a potent MCT-1 inhibitor, on alloimmune responses in the rat. METHODS In vitro activity was determined in a rat mixed lymphocyte(More)
We have recently described the immunosuppressive properties of AR-C117977 and AR-C122982, representatives of a group of compounds identified as inhibitors of lactate transporters (monocarboxylate transporters; MCTs). These compounds demonstrate the potential therapeutic usefulness of inhibiting MCT-1, but their physical and metabolic properties made them(More)
Current immunosuppressive therapies act on T lymphocytes by modulation of cytokine production, modulation of signaling pathways or by inhibition of the enzymes of nucleotide biosynthesis. We have identified a previously unknown series of immunomodulatory compounds that potently inhibit human and rat T lymphocyte proliferation in vitro and in vivo in(More)
Triggering innate immune responses through TLRs is expected to be a novel therapeutic strategy for the treatment of allergic diseases. TLR agonists are able to modulate Th2 immune responses through undefined mechanisms. We investigated the mechanism of action of the suppression of Th2 immune responses with a novel antedrug TLR7 agonist. The antedrug is(More)
Triggering innate immune responses through TLRs is expected to be a novel therapeutic strategy for the treatment of allergic diseases. TLR agonists are able to modulate Th2 immune responses through undefined mechanisms. We investigated the mechanism of action of the suppression of Th2 immune responses with a novel antedrug TLR7 agonist. The antedrug is(More)
TLR7 agonists modulate Th2 immune responses through mechanisms that have not been fully elucidated. Suppression of IL-5 production from Ag- or phytohemagglutinin-stimulated human PBMCs by the TLR7 antedrug AZ12441970 was mediated via type I IFN-dependent and type I IFN-independent mechanisms through TLR7 activation of plasmacytoid dendritic cells, B cells,(More)
AR-C117977, a monocarboxylate transporter inhibitor, reduces immune responses both in vitro and in vivo, maintains long-term graft survival, and induces operational tolerance. To evaluate the immunosuppressive limitations of AR-C117977, this study was performed in nonvascularized transplant models noted for their refractive response to standard(More)
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(More)
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