The Vanderbilt Center for Neuroscience Drug Discovery (VCNDD) has a mission to promote the translation of advances in basic science towards novel therapeutics. They have recruited faculty and staff with experience at over 10 different pharmaceutical companies to ensure a diverse set of approaches, techniques and philosophies to advancing compounds. Together they aim to de-risk drug discovery programs.
About the Target
Targeting metabotropic glutamate receptor 3 (mGlu3) has been linked as a potential therapeutic to many neurological disorders and well as oncology through the use of dual specific mGlu2/3 Antagonists (LY341495, RO4491533, MGS0039, RO4988546).
mGlu3 has been shown to regulate chemoresistance in glioma stem cells, in that the level of mGlu3 is inversely related to survival in patients with malignant gliomas (Cell Death and Differentiation, 2012, 1-12). The mechanism has been further studied to determine that mGlu3 negatively modulates BMP receptor signaling and increases the tumorigenic potential of glioma-initiating cells (Neuropharmacology 55, 2008, 568-576). Finally, the dual specific mGlu2/3 Antagonist LY341495 has been shown to enhance the chemosensitivity of colorectal cancer stem cells to standard cytotoxic chemotherapy (Neuroscience Poster, 2010, 642.28/E52).
- The VCNDD has developed proprietary highly selective CNS penetrant in vivo mGlu3 NAMs that are selective over mGlu2, unlike current competing compounds, which are non-selective.
- Low to moderate clearance has been observed with certain analogs in rat IV PK studies.
- Multiple compounds with clean P450 inhibition profiles have been identified.
- This is an earlier stage program, Hit to Lead Optimization.
Then only known competition is one dual mGlu2/3 NAM compound from Roche (decoglurant) is in the clinic, Phase II studies for Depression and Major Depressive Disorder.