Glutaminase inhibitors
We are seeking a co-development partner to support key in vivo data and drive rapid progression into clinical trials.
Highlights
- Potent (<10nM cells), selective and orally bioavailable allosteric inhibitors of GLS1
- Early lead compound CRT1 shows similar in vivo efficacy to CB-839
- Clean selectivity profile in safety panel
- Two new leads have been identified with improved PK and fold lower predicted human dosing
The opportunity
Cancer Research Horizons has developed a potent, selective and orally bioavailable series of small molecules inhibiting glutaminase (GLS), with superior developability.
GLS converts glutamine to glutamate, which feeds into the TCA cycle to provide building blocks for cellular survival. Many tumours show increased GLS1 levels and a dependence on glutamine, and extensive target validation work (both knockdown and inhibitor studies) have implicated GLS in multiple tumour types and suggest a role for GLS inhibitors in both combination and immune oncology settings.
Initial compounds showed good in vitro activity but were not sufficiently potent in vivo. However, the follow on lead series has been shown to have better PK properties, lower toxicity and a clean selectivity profile in vitro, predicting better results in vivo.
Patent applications covering both the original compound series and new lead series have been published and have extensive territory coverage.
Contact
Jonathan Brown is a Business Development Executive in the Business Development and Transaction team of Cancer Research Horizons. He spent the majority of his career in a variety of regional and global commercial roles at AstraZeneca, Roche and AbbVie.