# Novel Small Molecule Therapeutic for Vitiligo

> **NIH NIH R41** · AOHBIO CORPORATION · 2024 · $306,278

## Abstract

PROJECT SUMMARY/ABSTRACT
Vitiligo is characterized by the patchy loss of skin pigmentation that can adversely affect a person’s quality of life
and sense of well-being. Despite the prevalence of vitiligo [over 2 million U.S. citizens are affected by vitiligo and
the global cases range from 0.5% to 2% of the population], there is only one FDA-approved therapeutic for
vitiligo; a topical formulation of the Janus kinase (JAK)-inhibitor sold under the trade name Opzelura. Significant
shortcomings of Opzelura include: the limited response rate and the high cost. Thus, there is a critical need for
the development of novel therapeutics for vitiligo. The long-term research goal of this project is to discover and
develop safe and cost effective small organic compounds that can be used as therapeutics for vitiligo.
Investigations into the autoimmune mechanisms of vitiligo have revealed: (i) high levels of expression of the
cytokine CXCL10 at active sites of vitiligo in murine and human tissue; (ii) that inhibition of interferon-gamma
(IFN-γ) signaling, which induces CXCL10 expression, is protective from vitiligo in a murine model; and (iii) that
neutralization of CXCL10 can induce reversal of the disease in a murine model. These observations have led to
the conjecture that reagents which inhibit IFN-γ induced CXCL10 expression by keratinocytes, the main source
of CXCL10, could be developed into therapeutics for vitiligo.
The research team has identified a family of highly potent and specific inhibitors of glycogen synthase kinase-3
(GSK-3). The team recently discovered that COB-187, the lead compound within this family, inhibits IFN-γ
induced CXCL10 expression by human keratinocytes. These observations have led us to the following central
hypothesis: COB-187 is efficacious in vitiligo. To investigate this hypothesis, the following aims will be completed:
(i) to determine the ability of COB-187 to attenuate IFN-γ induced cytokine expression by human keratinocytes;
and (ii) to determine the mechanism by which COB-187 inhibits IFN-γ induced CXCL10 expression by
keratinocytes.
The family of compounds exemplified by COB-187 have the potential to become therapeutics for vitiligo. The
proposed work will provide a strong scientific foundation for the development of such therapeutics. Thus,
successful completion of these studies will have a positive impact on the large number of people who suffer from
vitiligo.

## Key facts

- **NIH application ID:** 11005527
- **Project number:** 1R41AR084965-01
- **Recipient organization:** AOHBIO CORPORATION
- **Principal Investigator:** Kelly McCall
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $306,278
- **Award type:** 1
- **Project period:** 2024-09-10 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11005527

## Citation

> US National Institutes of Health, RePORTER application 11005527, Novel Small Molecule Therapeutic for Vitiligo (1R41AR084965-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11005527. Licensed CC0.

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