Gotham Therapeutics and Mercachem announced the generation of a compound library for accelerated hit generation and hit-to-lead expansion against large parts of the epitranscriptomic target space. Using this library will further accelerate Gotham’s drug discovery efforts as the company expands its epitranscriptomics pipeline beyond the current lead program targeting the METTL3/METTL14 complex.
“Together with Mercachem, we have developed a unique approach to identify small-molecule master keys that are able to unlock novel targets and address the specific pharmacophoric features this target family shares,” said Dr. Gerhard Müller, Chief Scientific Officer of Gotham Therapeutics. “This targeted library further strengthens our drug discovery engine and will be repeatedly explored as we continue our collaboration with Mercachem in all future pipeline projects along the hit-to-lead candidate trajectory.”
“The growing epitranscriptomic-directed compound collection will enable Gotham to more rapidly advance drug discovery projects against novel targets,” said Dr. Frank Leemhuis, Managing Director of Mercachem. “We look forward to seeing the progress Gotham aims to make in the epitranscriptomic space with the assets and knowhow gleaned as part of our collaboration.”
As a result of the collaboration, over 2,000 analogues and over 80 distinct chemotypes have been produced, which clearly comprise several privileged structures for binding to epitranscriptomic targets, demonstrating and utilizing cross-target synergies within this target space. The consistent utilization of structure-based drug design combined with the excellence in scaffold design and library chemistry converged to yield several molecules with up to a thousand-fold increased affinity for some of the targets.