# Screening and Development of Small Molecule HDAC11 Inhibitors to Treat Obesity and Diabetes.

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2022 · $495,235

## Abstract

PROJECT SUMMARY/ABSTRACT
It is estimated that greater than 1/3 of the population of the United States is obese. Obesity is coupled to the
development of many chronic diseases, including type 2 diabetes (T2D), which is projected to afflict over half a
billion adults worldwide by 2040. Obesity is a consequence of a disparity between energy intake and
expenditure, and decreasing obesity requires a reduction in energy intake and/or an increase in energy
expenditure. Aside from diet and exercise, therapeutic interventions for obesity include bariatric surgery and
the use of drugs that decrease energy intake. There is intense interest in developing alternative
pharmacotherapy for obesity based on increasing energy expenditure via activation of brown adipose tissue
(BAT), or `beiging' of white adipose tissue (WAT). Our groups have a longstanding interest in the regulation
and function of a family of enzymes known as histone deacetylases (HDACs). During the course of our
investigations, we discovered that HDAC11 functions as a repressor of the thermogenic gene program in BAT,
and prevents beiging of WAT. Furthermore, we found that HDAC11 is not actually a deacetylase, but instead
functions as an efficient lysine defatty-acylase. Since HDAC11-deficient mice are healthy, and HDAC11 has
a unique catalytic activity compared to other HDAC isoforms, we hypothesize that selective HDAC11
inhibitors will increase energy expenditure and thus provide an innovative therapy for the treatment of obesity
and T2D. Three specific aims are designed to discover small molecules that selectively inhibit HDAC11
defatty-acylase activity.

## Key facts

- **NIH application ID:** 10319956
- **Project number:** 5R01DK119594-04
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Hening Lin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $495,235
- **Award type:** 5
- **Project period:** 2019-01-15 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10319956

## Citation

> US National Institutes of Health, RePORTER application 10319956, Screening and Development of Small Molecule HDAC11 Inhibitors to Treat Obesity and Diabetes. (5R01DK119594-04). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10319956. Licensed CC0.

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