JTE-607 (JTE607) is a multiple cytokine inhibitor that potently suppresses production of proinflammatory cytokines, targets pre-messenger RNA endonuclease cleavage and polyadenylation specificity factor 3 (CPSF3).
JTE-607 exhibits inhibitory activity on the growth of AML cell lines accompanying reduction of the proinflammatory cytokine and growth factor production.
JTE-607 suppressed expression and production of cytokines, which are spontaneously up-regulated in AML cell lines.
JTE-607 also abrogated proliferation of AML cells in a concentration range in which colony formation of normal bone marrow cells was not affected.
JTE-607 significantly prolonged survival in mice and reduced human cytokine mRNA levels in the bone marrow in leukemia model engrafted with U-937 cells.
Inhibition of CPSF3 by JTE-607 alters expression of known downstream effectors in AML and Ewing's sarcoma lines, upregulates apoptosis and causes tumor-selective stasis in mouse xenografts.
JTE-607 induces transcript accumulation and RNA Pol II read-through. CPSF3 is a core component of the pre-mRNA cleavage and polyadenylation complex.