Pannex’ Panx1 blocker platform
Pannex Therapeutics has designed a series of small molecule candidates that block Panx1, leveraging advanced in silico models and channel docking studies. These studies capitalize on the 3D structure of human Panx1, alongside our groundbreaking molecule PX001 and other established nonspecific Panx1 inhibitors. The in-silico screening process played a crucial role in identifying developability factors, toxicophoric groups, and metabolic liabilities, ensuring the creation of compounds that are not only effectively designed but also amenable to straightforward synthesis and structural adjustments.
All candidates are protected under a comprehensive composition of matter and use provisional patent, which was filed with the US Patent and Trademark Office (USPTO) in August 2022.
Following the design phase, selected compounds underwent synthesis and were subject to rigorous in vitro and in vivo screening processes.
Transwell Invasion Assay
Metastatic gene expression
Our Panx1 blockers show significant reduction in invasiveness and metastatic markers expression.
In vivo efficacy of selected leads in an Orthotopic MDA-MB-231-Luc breast cancer xenograft model in female BALB/c nude mice
The initiation of tumor growth suppression was observed early, achieving a reduction in tumor weight of up to 80% compared to the control group by intratumoral administration of the candidates.
Anti-metastasis efficacy of selected leads Orthotopic 4T1-Luc breast cancer syngeneic model in female BALB/c mice
The 4T1 cell line is one of the most aggressive, metastatic TNBC cell lines, resembling human stage IV breast cancer. The aim of this study was to prevent or reduce distal metastasis in mice.