# Developing novel therapeutics for the treatment of mastocytosis

> **NIH NIH R43** · NEMAGEN DISCOVERIES, INC · 2022 · $252,094

## Abstract

Abstract
Mastocytosis is a term used to describe a set of rare diseases that are characterized by increased mast cell
development and the enhanced presence of mast cells in various tissues and organs. Once activated, mast
cells promote inflammation through their robust production of histamines, leukotrienes, prostaglandins and
many other effector molecules that promote itching, burning, smooth muscle contraction and life-threatening
anaphylaxis, all of which are common symptoms of mastocytosis. Although patients suffering from
mastocytosis are prescribed antihistamines and mast cell stabilizers, treatment options are limited, and more
severe forms of the disease are extremely difficult to treat and remain life-threatening. Further, an incomplete
understanding of the factors that regulate mast cell development has dramatically limited the ability to
design novel therapeutics that selectively target mast cells. NemaGen’s published and preliminary studies
have revealed that the enzyme carbonic anhydrase (Car)1 is exclusively expressed by mast cell progenitors.
Further, we have demonstrated that small molecule-mediated inhibition of Car1 is sufficient to prevent murine
and human mast cell development. In addition, our data demonstrate that in vivo treatment with known
carbonic anhydrase inhibitors is sufficient to prevent mast cell development and inflammation in a murine
model of mastocytosis. Collectively, these studies suggest that Car1 represents a novel therapeutic target for
the treatment of mastocytosis and mast cell-mediated inflammation. Although existing carbonic anhydrase
inhibitors are available, our studies have shown that their effective doses far exceed those required for
translational applications. To address this, we have generated a strong team and effective workflow that allows
us to synthesize and test new Car enzyme inhibitors. Further, our data demonstrate that we can generate
significantly more effective inhibitors than currently available options. These exciting findings form the
foundation of this SBIR proposal and two specific aims: (i) Design, synthesize and optimize novel carbonic
anhydrase inhibitors. (ii) Evaluate the effects of Car enzyme inhibitors on enzymatic function and mast cell
development both in vitro and in vivo. Collectively, these pre-clinical studies will allow us to generate new Car
enzyme inhibitors for the treatment of mastocytosis and other mast cell-related disorders.

## Key facts

- **NIH application ID:** 10480408
- **Project number:** 1R43TR004219-01
- **Recipient organization:** NEMAGEN DISCOVERIES, INC
- **Principal Investigator:** Jianya Peng
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $252,094
- **Award type:** 1
- **Project period:** 2022-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10480408

## Citation

> US National Institutes of Health, RePORTER application 10480408, Developing novel therapeutics for the treatment of mastocytosis (1R43TR004219-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10480408. Licensed CC0.

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