# RXR Rexinoids for Cancer Chemoprevention

> **NIH NIH P01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2021 · $900,436

## Abstract

Non-melanoma skin cancers (NMSCs), (squamous cell carcinoma [SCC] and basal cell
carcinoma [BCC]), are major sources of morbidity in long term survivors of renal transplantation.
Due to medications these patients must take to prevent transplant rejection, NMSCs occur more
frequently (65-250x the general population for SCC; 10x for BCC), behave more aggressively,
and are more likely to metastasize than in the general population. Oral retinoids effectively protect
against NMSCs in these patients, but at dosages with unacceptable toxicity. Our team has
designed rexinoids with high specificity for the retinoid X receptor (RXR) without signaling through
RXR:LXR (liver X receptor) in the liver (or other RXR heterodimers). This eliminates the marked
hypertriglyceridemia that is the rate limiting toxicity of bexarotene, the only FDA approved RXR
binding rexinoid. Our lead compound, UAB30, prevents UV-induced NMSCs in animal models.
UAB30 has entered clinical trials in normal individuals and has shown no significant toxicity. We
hypothesize that UAB30 and other rexinoids that are based on UAB30's structure can be used as
highly effective, low toxicity chemopreventive agents limiting NMSCs in renal transplant
recipients. This Program brings together 7 researchers to carefully investigate mechanisms of
rexinoid chemoprevention of NMSCs, and to develop a systemic approach to translating the
scientific findings into new rexinoids for NMSC chemoprevention in renal transplant recipients.
The Program consists of 3 interactive Projects. Dr. Elmets (Proj. 1) will conduct a randomized,
double-blind, placebo-controlled study to identify biomarkers that can be employed as short term
predictors of efficacy for NMSC prevention in organ transplant recipients. Dr. Muccio (Proj. 2)
plans to design new rexinoids with the needed steric bulk in the ring region of the rexinoid to act
as an agonist, but without the steric bulk in critical regions that are believed to stimulate signaling
that induces lipid synthesis. Dr. Kedishvili (Proj. 3) will examine whether rexinoids potentiate the
transcriptional activity of existing endogenous all-trans-retinoic acid (ATRA) mediated by
RXR/RAR heterodimers, which, in turn, leads to further upregulation of ATRA levels. The Projects
will be supported by 3 Cores (Administrative; Design and Synthesis; Rexinoid Screening and
Animal). Scientists involved in the Program have a long history of collaboration and are joined by
shared interests in rexinoid chemistry, biochemistry, cancer chemoprevention and translational
science.

## Key facts

- **NIH application ID:** 10263919
- **Project number:** 5P01CA210946-05
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Craig A Elmets
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $900,436
- **Award type:** 5
- **Project period:** 2017-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10263919

## Citation

> US National Institutes of Health, RePORTER application 10263919, RXR Rexinoids for Cancer Chemoprevention (5P01CA210946-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10263919. Licensed CC0.

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