# Small molecules for expansion of islet beta-cell mass in diabetes

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $670,806

## Abstract

Project Abstract/Summary
Diabetes currently affects 9.3% of the U.S. population totaling $245 billion annually in U.S. healthcare costs.
Current therapies for diabetes are limited in their ability to control blood glucose and/or enhance insulin
sensitivity. Given the magnitude of diabetes costs and complications, new therapies with reduced side effects
are urgently needed. The common defect in both type 1 and type 2 diabetes is the loss of functional pancreatic
islet -cell mass. A therapeutic intervention that replenishes the insulin-producing pancreatic beta cells
represents a cure for diabetes
We propose to develop two distinct molecular scaffolds with demonstrated in vivo proof of concept for stimulating
pancreatic beta-cell proliferation. A series of phenylbenzamides, discovered in an unrelated hepatic steatosis
screen, were found to stimulate selective beta cell proliferation in rodents, isolated rat and human islets, and will
be evaluated and optimized for efficacy and translational potential. The second series - chromenones,
discovered in a Nkx6.1 promoter screen, have been shown to robustly stimulate beta-cell proliferation in rodent
and human islets. We will perform medicinal chemistry optimization on both scaffolds to produce in vivo chemical
probes with translational potential for human therapeutic use.

## Key facts

- **NIH application ID:** 9902446
- **Project number:** 5R01DK120623-02
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** CHRISTOPHER B NEWGARD
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $670,806
- **Award type:** 5
- **Project period:** 2019-04-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9902446

## Citation

> US National Institutes of Health, RePORTER application 9902446, Small molecules for expansion of islet beta-cell mass in diabetes (5R01DK120623-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9902446. Licensed CC0.

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