# Molecular basis of the anti-cancer and anti-inflammation activities of JTE607

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA-IRVINE · 2021 · $235,500

## Abstract

Project Summary:
The small molecule drug JTE-607 was discovered 20 years ago that inhibits the production of
pro-inflammatory cytokines. Animal studies showed that JTE-607 can be used to treat multiple
inflammation diseases, including septic shock, acute injury, and endotoxemia, and it has
progressed through healthy human volunteer clinical studies. More recently it was discovered that
this compound also displays anti-tumor activities. It is particularly potent against acute myeloid
leukemia (AML) and Ewing’s sarcoma. Despite these promising pharmacological studies, the
mechanism of action of JTE-607 remained unknown until recently. Two studies published recently
revealed that JTE-607 is a prodrug that is converted to Compound 2 (Cmp2) in cells, which
specifically binds to the CPSF73 protein, an essential mRNA 3’ end processing factor. The 3’
ends of almost all eukaryotic mRNAs are formed in two catalytic steps, an endonucleolytic
cleavage and the addition of a string of adenosines (polyadenylation). CPSF73 is the
endonuclease responsible for the cleavage step. It has been proposed that JTE-607 kills cancer
cells by inducing mRNA 3’ processing and transcription termination defects, which, in turn, cause
genome instability and cell death. However, JTE-607 has not been directly tested in human mRNA
3’ processing and it is unclear why JTE-607 only targets specific cancer types. We aim to identify
the RNA sequences and the protein “sensors” that determine the drug sensitivity.These studies
will reveal the in-depth mechanism of action of a novel anti-inflammation and anti-cancer
compound. Characterization of the JTE-607-resistant mRNA 3’ processing may identify novel
target(s) for blocking mRNA 3’ processing in future drug development. From the perspective of
basic science, JTE-607 provides a unique tool for dissecting the mechanism of mRNA 3’
processing and the discovery of multiple modes of mRNA 3’ processing will have implications for
our fundamental understanding of eukaryotic gene expression.

## Key facts

- **NIH application ID:** 10354133
- **Project number:** 1R21AI166703-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Yongsheng Shi
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $235,500
- **Award type:** 1
- **Project period:** 2021-09-24 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10354133

## Citation

> US National Institutes of Health, RePORTER application 10354133, Molecular basis of the anti-cancer and anti-inflammation activities of JTE607 (1R21AI166703-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10354133. Licensed CC0.

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