# Novel Orally Available CBP/Beta-Catenin Antagonists to Treat Idiopathic Pulmonary Fibrosis

> **NIH NIH R43** · 3+2 PHARMA, LLC · 2022 · $334,008

## Abstract

PROJECT SUMMARY/ABSRACT
 Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic, progressive fibrosing interstitial pneumonia
characterized by the formation of scar tissue within the lungs in the absence of any known cause. IPF is a
devastating disease with a poor prognosis and a median survival time of 2–4 years. The natural history of IPF is
heterogeneous and most patients follow a slowly declining clinical course after diagnosis. However, episodes of
acute respiratory worsening, are experienced by a significant minority.
 Currently there are two drugs approved by the FDA for the treatment of IPF, Boehringer Ingelheim's
nintedanib and Roche's pirfenidone. Both drugs only modestly slow development of scar tissue in lungs of IPF
patients. However, neither can reverse nor even halt disease progression, as they merely serve to slow the
decline in patients' lung function. Therefore, there is a great unmet need to develop new therapeutics for IPF
patients that can minimally stabilize and potentially reverse the course of the disease. Additionally, many patients
with severe COVID-19 infections with comorbidities, subsequently develop pulmonary fibrotic disease1 and
activation of Wnt/β-catenin signaling is associated with ventilator- induced pulmonary fibrosis2.
 IPF is a disease caused by injury to alveolar epithelial cells (AECs) with subsequent aberrant repair and
over activation of mesenchymal cells with the formation of fibroblastic and myofibroblastic foci. It is well
documented that Wnt/β-catenin signaling is important in the survival, migration, and proliferation of AECs and
activated Wnt/β-catenin signaling in fibroblasts increases migration, proliferation, and extracellular matrix (e.g.
collagen) production. However, the role of β-catenin signaling in fibrosis appears to follow a “Goldilocks” model,
 where too little β-catenin signaling
 in AT2 cells promotes epithelial
 cell death thereby exacerbating
 lung injury and fibrosis, whereas
 aberrantly high β-catenin
 signaling enhances the fibrotic
 phenotype via fibroproliferation,
 migration, and activation.
 Furthermore, the fate of “good”
 versus “bad” β-catenin signaling is
 dictated by β-catenin’s differential
 coactivator usage (Fig. 1)3.
 Therefore, safe modulation of
 Wnt/β-catenin signaling is a very
 appealing therapeutic strategy to
 treat pulmonary fibrosis. To date,
 there are no such molecularly
 targeted drugs that modulate
 Wnt/β-catenin signaling and
 differential Kat3 (i.e. CBP and
 p300) coactivator usage, for IPF in
 clinical trials.
 The proposed research plan
 outlines the development of a
potent and highly specific small molecule, orally available, CBP/β-catenin antagonist, [3+2]-517. This lead
compound and drug candidate demonstrates promising activity in the bleomycin induced mouse model of fibrosis
when dosed orally. The proposed research centers on in vivo evaluation of [3+2]-517 to reverse late stage
pulmonary fibrosis and to develop a highly efficient and...

## Key facts

- **NIH application ID:** 10480363
- **Project number:** 1R43HL160312-01A1
- **Recipient organization:** 3+2 PHARMA, LLC
- **Principal Investigator:** Omar Haffar
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $334,008
- **Award type:** 1
- **Project period:** 2022-03-05 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10480363

## Citation

> US National Institutes of Health, RePORTER application 10480363, Novel Orally Available CBP/Beta-Catenin Antagonists to Treat Idiopathic Pulmonary Fibrosis (1R43HL160312-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10480363. Licensed CC0.

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