JTE-607

JTE-607 inhibits inflammatory cytokine production in human peripheral blood mononuclear cells (PBMC’s) without causing immunosuppression: IC50’s = 11 nM (TNF-), 5.9 nM (IL-1), 8.8 nM (IL-6), 7.3 nM (IL-8), and 9.1 nM (IL-10) .1 It displayed efficacy in a mouse model of septic shock.2 JTE-607 also showed inhibitory activity against acute myelogenous leukemia cell lines.3,4 Recently, the mechanism of action of JTE-607 (a pro-drug, with the active species being the free acid) has been found to be inhibition of pre-messenger RNA endonuclease Cleavage and Polyadenylation Specificity Factor 3 (CPSF3) .5,6 This prevents release of newly synthesized mRNA’s resulting in read-through transcription and the formation of DNA-RNA hybrid R-loop structures. Transcripts down-regulated by JTE-607 were related to DNA damage-based phenotype