JTE-607

JTE-607 (also known as TO-207) is a small molecule prodrug that undergoes ester hydrolysis by carboxylesterase 1 (CES1) to form its active metabolite. The active form of JTE-607 directly binds to and inhibits cleavage and polyadenylation specificity factor subunit 3 (CPSF3, also known as CPSF73), an essential endonuclease involved in the 3'-end processing of pre-messenger RNA (pre-mRNA). By blocking CPSF3, JTE-607 inhibits pre-mRNA cleavage and polyadenylation, leading to the accumulation of unprocessed pre-mRNAs and transcriptional readthrough. This mechanism selectively suppresses the production of multiple pro-inflammatory cytokines (including TNF-alpha, IL-1beta, IL-6, IL-8, and IL-10) in monocytes and macrophages. Additionally, JTE-607 induces S-phase cell cycle arrest and apoptosis in various cancer cells, particularly acute myeloid leukemia (AML), Ewing's sarcoma, and pancreatic ductal adenocarcinoma (PDAC). It has also been investigated as a potential antiviral agent against hepatitis B virus (HBV) by triggering viral transcriptional readthrough and destabilizing HBV RNAs, and as a countermeasure for acute radiation syndrome (ARS).

Other names

JTE-607 dihydrochlorideJTE607 dihydrochlorideJTE 607 dihydrochlorideJTE-607 free baseJTE607 free baseJTE 607 free base