(R)-Lisofylline

(R)-Lisofylline ((R)-Lisophylline) is a (R)-enantiomer of the metabolite of Pentoxifylline with anti-inflammatory properties. (R)-Lisofylline is a lysophosphatidic acid acyltransferase inhibitor with an IC₅₀ of 0.6 µM and interrupts IL-12 signaling-mediated STAT4 activation. (R)-Lisofylline has the potential for type 1 diabetes, autoimmune disorders research^[1][2]. IC50 & Target: IC50: 0.6 µM (Lysophosphatidic acid acyltransferase)^[1]
STAT4^[1] In Vitro: (R)-Lisofylline blocks IL-12-driven Th1 differentiation and T cell proliferation in vitro, yet has no effect on IL-12 secretion from APCs ex vivo or in vitro^[3]. In Vivo: (R)-Lisofylline reduces the impairment of insulin secretion induced by IL-1β in cultured rat islet cells, suppresses IFN-γ production, the onset of diabetes, and macrophage infiltration into islets from NOD mice, as well as Lisofylline improves insulin response and lowers glucose levels in Streptozotocin-treated rats after the oral glucose tolerance test^[1].
(R)-Lisofylline prevents β cell dysfunction in NOD mice by inhibition of STAT4 phosphorylation which interrupts IL-12 signaling. (R)-Lisofylline ameliorates experimental allergic encephalomyelitis in mice^[1].
(R)-Lisofylline also improves survival in mice injected with a lethal dose of LPS and ameliorates sepsis-induced lung injury in minipigs. In rats given IL-1 intratracheally (R)-Lisofylline pretreatment reduces lung leak but does not decrease neutrophil accumulation in lungs^[1].
(R)-Lisofylline also suppresses release of TNF-α in vivo in mice and ex vivo in human blood stimulated with endotoxin derived from Salmonella or Escherichia coli^[1].