GLUT1/3 Inhibitors for the Treatment of Autoimmune Diseases and beyond
Prof. Herbert Waldmann, Max-Planck-Institute for Molecular Physiology
Lead Discovery Center
Our plan is to setup a new venture around our GLUT1/3 inhibitor program. The overall idea is to exploit the full potential of this platform to develop inhibitors in the areas of immune disorders, oncology, psoriasis and infectious diseases. We are confident that the two existing inhibitor series can deliver several staring points to differentiate the chemical programs when required.
Basic principle: There is a cell-type specific dependency of Teff and Treg on glucose metabolism upon activation. In addition a selective and rapid upregulation of GLUT1/3 upon activation (CD3/28) can be found. GLUT-1-KO blocks Teff function & proliferation while leaving Treg unaffected. Treg rely on alternative energy sources for proliferation such as fatty acid uptake and oxidation
Hypothesis: Restoration of overshooting immune response (Teff/Treg imbalance) by selective GLUT-1/3 blockade.
Currently we have 2 series of inhibitors under investigation. A frontrunner from one of the series has been nominated as lead showing proof of efficacy in a relevant animal model.
We are looking for partners (corporate and/or venture) that want to join us setting up a spin-off to leverage the full potential of our portfolio of inhibitors here.
Lead nomination completed in the field of immune disorders, upside potential during lead optimization to branch into oncology, psoriasis, infectious diseases.
Patent application filed, two more patent applications in preparation
Reckzeh, Waldmann, Small-Molecule Inhibition of Glucoe Trasporter GLUT1-4; ChemBioChem 2020, 21, 45-52