# A Novel Small Molecule for The Prevention and Treatment of Diabetic Retinopathy

> **NIH NIH R43** · EXCITANT THERAPEUTICS, LLC · 2020 · $271,325

## Abstract

SUMMARY
Diabetic retinopathy (DR) is a common complication of diabetes and a leading cause of blindness among
working-age adults around the world. Currently, there is no non-invasive treatment demonstrated to fully blunt
DR progression. Thus, a new drug for long-term prevention and treatment is urgently needed to improve the
management for DR. Recently, two independent prospective clinical trials (FIELD and ACCORD) have identified
that fenofibrate (a PPARα agonist) has unprecedented therapeutic effects in DR. Our previous experiment has
confirmed PPARα down-regulation induced by diabetes plays a key pathogenic role in DR, further suggesting
that PPARα is a promising drug target for DR. However, fenofibrates is a low potency PPARα agonist, which
makes it not an ideal treatment option for DR and has not been approved as an anti-DR drug by FDA. Therefore,
the development of novel oral drugs using PPARα agonists is an unmet clinical need. Recently, our team has
independently designed, synthesized and screened more than 200 novel small molecule compounds, with
different crystal structures from fenofibrate using PPARα 3D modeling. A190(EC50 = ∼27 nM) is selected as the
leader compound since it possesses significant PPAR α agonist feature. A190 exhibited improved potency for
PPARα agonism (~2700 fold higher than its parent compound Y-0452 EC50 = ∼50 µM and fenofibrate).
Importantly, A190 has also proven to be potentially more effective than fenofibrate in the protection of retinal
neurons and vascular cells in vitro. These findings suggest that A190 is a novel PPARα agonist with higher
therapeutic potential for DR than fenofibrate. This project will serve as a proof-of-concept study to investigate
the effects of the novel PPARα agonist A190 in a diabetic animal model. The program includes two specific aims.
1: Determine whether A190 reduces retinal inflammation and vascular leakage in a diabetic model. 2: Determine
whether A190 protects retinal neurons in a diabetic model. This SBIR Phase I project will evaluate the effect of
this novel PPARα agonist A190 on retinal oxidative stress, inflammation, neuron apoptosis and vascular leakage
in a diabetic animal model, and lay a solid groundwork for future development of this drug candidate, such as
pharmacokinetic (PK) and safety studies, in the Phase II preclinical studies.

## Key facts

- **NIH application ID:** 10080648
- **Project number:** 1R43EY032023-01
- **Recipient organization:** EXCITANT THERAPEUTICS, LLC
- **Principal Investigator:** Yuhong Anna Wang
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $271,325
- **Award type:** 1
- **Project period:** 2020-09-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10080648

## Citation

> US National Institutes of Health, RePORTER application 10080648, A Novel Small Molecule for The Prevention and Treatment of Diabetic Retinopathy (1R43EY032023-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10080648. Licensed CC0.

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