# Development of lysosome targeted therapeutics

> **NIH NIH R41** · MAJESTIC THERAPEUTICS, LLC · 2022 · $258,341

## Abstract

Project Summary/Abstract
Lysosomal proteolysis facilitates the turnover of organelles and selected long-lived proteins and is a critical
regulator of cellular homeostasis. Its aberrant activation promotes drug resistance and cancer progression by
generating alternative sources of survival sustaining metabolic fuel to cells that are stressed by hypoxia,
radiation, chemotherapy, and targeted agents. Despite its clear potential as a therapeutic target, no intentionally
designed targeted inhibitors of lysosomal function have been FDA approved to date. We recently generated a
series of novel orally available lysosomal disrupting agents with favorable safety profiles and single agent
therapeutic activity. Our first lead hit is active against acute myeloid leukemia (AML) cells with high-risk features
and augments the efficacy of azacitidine to significantly extend overall survival in mouse models of AML. Our
major goal is to use medicinal chemistry approaches to optimize its pharmacologic properties to develop a novel
lysosomal proteolysis inhibitor that can be commercialized for the treatment of patients with AML and other
diseases where aberrant pathway activity contributes to pathogenesis.

## Key facts

- **NIH application ID:** 10482643
- **Project number:** 1R41CA271967-01
- **Recipient organization:** MAJESTIC THERAPEUTICS, LLC
- **Principal Investigator:** Jennifer S Carew
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $258,341
- **Award type:** 1
- **Project period:** 2022-07-01 → 2023-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10482643

## Citation

> US National Institutes of Health, RePORTER application 10482643, Development of lysosome targeted therapeutics (1R41CA271967-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10482643. Licensed CC0.

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