# Identifying primary targets of bumped kinase inhibitor derived compounds to improve utility as therapy for castration resistant prostate cancer

> **NIH NIH R21** · UNIVERSITY OF WASHINGTON · 2021 · $206,284

## Abstract

Project Summary/Abstract
Castration-resistant prostate cancer (CRPC) that inevitably escapes primary therapies most often retains
dependency on androgen receptor (AR). We are repositioning bumped kinase inhibitors (BKIs), originally
designed to inhibit Toxoplasma gondii and Cryptosporidium parvum. A class of BKI-derived compounds
(BKIDCs) target lethal CRPC by blocking androgen receptor (AR) signaling, placing AR positive CRPC cells in
G1 cell cycle arrest to block their proliferation, and inhibiting glycolysis-derived ATP production. Moreover, our
safety and pharmacokinetics data indicate that BKIDCs are compounds that can be reasonably developed as a
drug for the treatment of CRPC. Importantly, structure–activity relationship studies revealed that BKIDCs
appear to exhibit their antiproliferative activities in prostate cancer through off-target effects (not necessarily as
kinase inhibitors), which warrants further investigation of their mechanism of action (MOA). In this proposal we
will determine the primary sites of BKIDCs’ action in AR-positive prostate cancer cell lines through both
hypothesis-driven and unbiased “-Omics” approaches. We will further validate and characterize potential
targets by pharmacological and genetic manipulation. By completing the proposed studies, we will learn MOA
of BKIDCs and be ready to take further steps to bring BKIDCs to clinic.

## Key facts

- **NIH application ID:** 10106409
- **Project number:** 1R21CA255830-01
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Takuma Uo
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $206,284
- **Award type:** 1
- **Project period:** 2021-01-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10106409

## Citation

> US National Institutes of Health, RePORTER application 10106409, Identifying primary targets of bumped kinase inhibitor derived compounds to improve utility as therapy for castration resistant prostate cancer (1R21CA255830-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10106409. Licensed CC0.

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