# Development of the Next Generation of FABP5 Inhibitors to Treat Prostate Cancer

> **NIH NIH R01** · STATE UNIVERSITY NEW YORK STONY BROOK · 2024 · $629,362

## Abstract

Project Summary
Despite advances in anti-androgen and taxane-based therapies, prostate cancer (PC) often becomes
castration-resistant, metastatic, and incurable. Consequently, there is an urgent need to develop novel
interventions to treat metastatic PC. Lipid signaling and metabolism are major drivers of PC metastasis and
present ideal targets for therapeutic intervention. However, therapeutic exploitation of lipid signaling systems is
hampered by the existence of multiple lipid metabolizing enzymes and nuclear receptors, which would
necessitate targeting these systems in parallel. Fatty acid binding protein 5 (FABP5) is an intracellular carrier
that shuttles bioactive lipids to nuclear receptors, thereby activating gene transcription programs that enhance
tumor growth and metastasis. FABP5 is not expressed in the normal prostate but becomes highly upregulated
in advanced metastatic PC. Our group has obtained preliminary data demonstrating that FABP5 is
indispensable for the delivery of pro-tumorigenic lipids produced by multiple cytosolic to nuclear receptors to
promote PC metastasis. This positions FABP5 as an essential node in a PC lipid signaling network and an
attractive target for the development of therapeutics to treat metastatic PC. Despite the considerable promise
of FABP5 inhibitors as potential PC therapeutics, potent and selective inhibitors have yet to emerge. The major
goal of this proposal is to develop and optimize novel potent and selective FABP5 inhibitors. The proposed
multidisciplinary project will be carried out by a highly qualified team with expertise in computer-aided drug
design, medicinal chemistry, and PC biology. Aim 1 will leverage structure-based drug design and iterative
chemical synthesis approaches to identify and optimize FABP5 inhibitors for potency and selectivity. Aim 2 will
employ a robust in vitro inhibitor testing platform including assessments of inhibitor potency, efficacy,
selectivity, stability, and cytotoxicity in PC cell-lines and non-transformed cells. Aim 3 will assess the efficacy of
candidate inhibitors in mouse models of PC, including a novel genetically engineered mouse model of
androgen-dependent and castration-resistant PC. We will also assess the efficacy of FABP5 inhibitors when
used as monotherapies and in combination with FDA approved therapeutics. Successful completion of the
proposed studies will lead to the development of optimized FABP5 inhibitor scaffolds that can be advanced to
late stage IND-enabling studies and eventual clinical deployment.

## Key facts

- **NIH application ID:** 10775710
- **Project number:** 5R01CA237154-05
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **Principal Investigator:** Martin Kaczocha
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $629,362
- **Award type:** 5
- **Project period:** 2020-02-01 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10775710

## Citation

> US National Institutes of Health, RePORTER application 10775710, Development of the Next Generation of FABP5 Inhibitors to Treat Prostate Cancer (5R01CA237154-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10775710. Licensed CC0.

---

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