# Preclinical characterization of saracatinib  for cystic fibrosis therapy

> **NIH NIH UH3** · CINCINNATI CHILDRENS HOSP MED CTR · 2020 · $357,751

## Abstract

Cystic Fibrosis (CF), caused by mutations in the cystic fibrosis transmembrane conductance
regulator (CFTR) gene, is a life-limiting inherited disorder affecting 70,000 individuals worldwide
(~30,000 in the US) with annual health care costs of at least $1.8 billion. Recent advances in new
CF drug development have led to approval of ivacaftor (Kalydeco or VX770), lumacaftor/ivacaftor
combination (Orkambi or VX809+ VX770), and tezacaftor/ivacaftor (Symdeko or VX661+VX770)
under review). Although these represent exciting translational successes for the CF community,
their clinical efficacy for patients with CF is suboptimal and falls within the range of established
symptomatic therapies. Furthermore, persistent airway infection and inflammation may
undermine benefits of current CFTR modulators, including enhanced degradation of corrected
Phe508del-CFTR by Pseudomonas aeruginosa virulence factors. Finally, the high cost of CFTR
modulators limits access of CF patients to CFTR modulators, highlighting the critical need for
ongoing effective drug development. Our combinatorial bioinformatics analysis using CF patient
gene expression data coupled with compound screening and in vitro assays identified saracatinib
(AZD0530), a known src family kinase (SFK) inhibitor, as a candidate CFTR modulator eliciting a
strong rescue of F508del-CFTR comparable to that of approved CFTR modulators. Several prior
studies have also demonstrated anti-inflammatory and anti-infective activity of saracatinib. This
proposal is designed to determine if saracatinib is a candidate therapeutic for CF, and its primary
mechanism of action relevant to CF lung disease in vivo. Our three specific aims are: aim 1:
Establish saracatinib as a pre-clinical CFTR modulator (UG3); aim 2: Evaluate the effect of
saracatinib on infection and inflammation associated with CF (UG3); and aim 3: Prepare for a
clinical trial to test effectiveness of saracatinib for CF therapy (UH3). The ultimate goal of this
project is to provide evidence in support of a multi-center clinical trial of saracatinib in CF.

## Key facts

- **NIH application ID:** 10153165
- **Project number:** 4UH3TR002612-03
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** Gary Lewis McPhail
- **Activity code:** UH3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $357,751
- **Award type:** 4N
- **Project period:** 2018-09-15 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10153165

## Citation

> US National Institutes of Health, RePORTER application 10153165, Preclinical characterization of saracatinib  for cystic fibrosis therapy (4UH3TR002612-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10153165. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*