# 1,3-Thioureas as First In Class Mitochondrial Inhibitors to Treat Oral Cancer

> **NIH NIH R41** · KERACEUTICALS, INC. · 2024 · $399,635

## Abstract

Abstract
Keraceuticals is developing a patent-protected novel class of anticancer drugs called 1,3-thioureas for the
treatment of oral squamous cell carcinoma (OSCC). OSCC is the most common oral malignancy, accounting for
80–90% of all oral cancers and 60% of all cases of head and neck squamous cell carcinoma (HNSCC). Among
all types of HNSCC, OSCC has the highest recurrence rates and lowest median survival. Even with additional
treatment, the survival rate for recurrent OSCC is a mere 6-7 months. Patient outcomes for OSCC have not
changed in 50 years, due in part to the fact that no targeted therapies have been developed for advanced and
recurrent OSCC. Thus, there is a significant unmet need to identify and develop novel therapies to treat OSCC.
In response to this need, Keraceuticals developed 1,3-thioureas that demonstrate potent antiproliferative effects
against a panel of cancer types including OSCC, non-small cell lung cancer, breast, prostate, brain, and
endometrial cancer in vitro. 1,3-thioureas inhibit oxidative phosphorylation (OXPHOS) and calcium homeostasis
in cancers providing a one-two punch that results in endoplasmic reticulum stress, mitochondrial membrane
depolarization, and subsequent reactive oxygen species-driven apoptosis selectively in tumor cells.
Keraceuticals’ lead compound, CIDD99 has shown promising results in OSCC cell lines, and significantly
reduced tumor volumes (5-fold) in OSCC mouse xenograft models when administered intraperitoneally.
However, additional R&D is required to develop formulations for oral and/or intravenous administration of
CIDD99 and to determine the bioavailability of subsequent PK and tissue distribution prior to initiating
manufacturing, full-scale toxicology studies, and clinical trials. This Phase I project proposes the following Aims:
1. Formulate CIDD99 for oral and/or IV administration. Rapid assessment of these oral and/or IV formulations
will be performed on blood from non-tumor-bearing mice and enable fast identification of appropriate formulations
for larger efficacy studies, comprehensive PK studies, and tissue distribution analyses. Formulations with equal
or improved blood concentrations will be utilized in Aim 2. 2. Confirm formulated CIDD99 efficacy and compare
against standards of care in mouse OSCC models. The most efficacious formulation will be evaluated as a lone
treatment or in combination with cisplatin or the epidermal growth factor receptor (EGFR) inhibitors cetuximab
and gefitinib. Lastly, tongue tumor models will be used to assess metastatic disease. Effects on tumor growth,
nodal disease, tolerability, tissue distribution, and histopathology will be assessed, and initial toxicity analyses
will be performed. These key studies will verify efficacy of formulations that enable oral and/or IV administration
for future clinical trials. Mechanistic effects on in vivo EGFR signaling, apoptosis, and markers of epithelial
mesenchymal transition will also be evaluated. The abo...

## Key facts

- **NIH application ID:** 11006942
- **Project number:** 1R41DE034719-01A1
- **Recipient organization:** KERACEUTICALS, INC.
- **Principal Investigator:** Cara B Gonzales
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $399,635
- **Award type:** 1
- **Project period:** 2024-09-25 → 2026-09-24

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11006942

## Citation

> US National Institutes of Health, RePORTER application 11006942, 1,3-Thioureas as First In Class Mitochondrial Inhibitors to Treat Oral Cancer (1R41DE034719-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/11006942. Licensed CC0.

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