# Elucidating the mode of action of the abietanes to develop potential therapeutic agents

> **NIH NIH R15** · LOUISIANA STATE UNIV A&M COL BATON ROUGE · 2022 · $411,836

## Abstract

PROJECT ABSTRACT
 Over expression of eukaryotic initiation factors (eIFs) has been reported in various human diseases
including breast cancer (BC). Our objective is to develop tool compounds based on the abietane natural products
to selectively target eIFs. Approximately 15-20% breast cancer cases are characterized as triple negative breast
cancer (TNBC), a subtype that lacks effective targeted therapy modalities,1 and is often plagued with
dysfunctional eIFs expression.2 Therefore, there is a need to discover new chemical matter that could selectively
targeted TNBC to reduce mortality rates associated with this disease.
 We have shown that abietane natural product derivatives (SJ38) significantly reduce protein synthesis
and target eIF2/eIF4 signaling axis in TNBC cellular models. We discovered that a) SJ38 selectively inhibits
cancer cell viability at the low micromolar range (<10μM) while not affecting non-cancerous mammary epithelial
cell viability or signaling, b) SJ38 significantly reduces the expression of regulatory factors involved in protein
synthesis, and c) Stable isotope labeling with amino acids in cell culture (SILAC) proteomics provided Gene
Ontology analysis that SJ38 mainly targeted protein synthesis and Ingenuity Pathway Analysis suggested that
SJ38 exerts its anticancer effects primarily through the eIF2, and eIF4/p70S6K signaling pathway.
Our long-term goal is to elucidate SJ38 molecular mechanism in TNBC focusing on translational control. Our
study addresses a gap in knowledge to discover new therapeutic agents and biological targets to potentially treat
TNBC. We hypothesize that SJ38 reduces breast cancer progression and sensitizes cells to therapy via
translational control. We propose the following specific aims: 1) Develop a novel synthetic strategy to access a
series of diverse abietane derivatives to facilitate structure activity relationship (SAR), and target engagement
studies. 2) Determine the biological properties of the generated compounds as protein synthesis modulators and
their capability to inhibit proliferation and migration in TNBC cellular models. 3) Identify the mechanism by which
the abietanes target cancer cellular models.
IMPACT: Results from the proposed studies will provide critical knowledge towards the development of targeted
therapeutic strategies needed for the successful treatment of human diseases including cancer.

## Key facts

- **NIH application ID:** 10580286
- **Project number:** 1R15GM148983-01
- **Recipient organization:** LOUISIANA STATE UNIV A&M COL BATON ROUGE
- **Principal Investigator:** Fatima R Rivas
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $411,836
- **Award type:** 1
- **Project period:** 2022-09-15 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10580286

## Citation

> US National Institutes of Health, RePORTER application 10580286, Elucidating the mode of action of the abietanes to develop potential therapeutic agents (1R15GM148983-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10580286. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*