Case study: Repurposing of PI3K pathway modulators for PHTS
Introduction
PTEN Research partnered with two leading drug discovery and development Contract Research Organisations (CROs) to undertake basic and translational contract research activities focused on drug repurposing studies.
Key facts
Project title: Preclinical Repurposing of PI3K Pathway Modulators for PHTS
Type of study: Preclinical - PHTS model development and testing to support drug repurposing
Contract Research Organisations (CROs):
Evotec – headquarters in Hamburg, Germany
Charles River Laboratories – headquarters in Wilmington, MA, USA
Project start: October 2020 Completed: Q1 2026
Project goals
Development of in vitro and in vivo models for pre-clinical drug-repurposing screens to uncover new treatment options for PHTS.
Project overview
A number of bespoke in vitro models have been established to identify candidates for in vivo evaluation in models representing PHTS neurodevelopmental delay and autism (Evotec), and vascular anomalies and tissue overgrowth (Charles River Laboratories). Our current focus is on repurposing small molecules targeting the PI3K pathway and other pathways of interest.
These research activities are managed by joint PTEN Research and CRO steering committees, with input from independent experts and oversight from the Trustees.
Outcomes
In addition to identifying potential drug repurposing candidates for clinical testing, it is hoped that studying these models will also allow us to develop valuable insights into the dysregulated signalling that results from PTEN mutations, and the relative importance of PI3K and other pathways to the different phenotypes associated with PHTS.
Repurposing projects with both companies have been completed. The following publication resulted from the work with Evotec:
Repurposing drugs for treating the neurobehavioral manifestations of PTEN hamartoma tumour syndrome.
A similar publication summarising the work with Charles River Laboratories is in preparation.
More information about the CROs can be found on their corporate websites.
