Completion of Gene-to-Lead phase for first discovery project targeting METTL3/METTL14 complex
Gotham Therapeutics has selected ZoBio to initiate a collaboration on the development of small molecules targeting epitranscriptomic targets. This collaboration has now resulted in several lead candidates for the METTL3/METTL14 complex.
With 15 years of experience, ZoBio is the proven partner for biophysics driven, fragment based drug discovery. We are dedicated to achieving the best science and highest level of transparency.
Our integrated discovery engine progresses projects from gene-to-lead. High throughput protein engineering and production, diverse, novel fragment libraries, proprietary biophysical screening technologies and complementary structural biology approaches have been tailored to provide validated data at every step of the process. The right combination of these various disciplines generates actionable medicinal chemistry hypotheses for small molecule modulators of a great variety of pharmacological targets, including those that have previously been out of reach.
‘In a sector that is still in its infancy, we have made tangible progress with our partner ZoBio to develop small molecule leads against a portfolio of epitranscriptomic targets just 14 months after initiation of the project,’ commented Dr. Lee Babiss, Chief Executive Officer of Gotham Therapeutics. ‘Today’s news is also a validation of the semi-virtual model we use and the productivity of our network with best-in-class CROs.’
‘With METTL3/METTL14 being among the more obvious approaches in epitranscriptomics, the quality of the hit matter pursued is going to be a key differentiating factor,’ added Dr, Gerhard Müller, Chief Scientific Officer of Gotham Therapeutics. ‘Together with ZoBio, we have not just successfully identified the initial candidates for Gotham’s first pipeline program but also established a robust process from gene to lead as a platform for additional projects to come.’
In January 2018, Gotham Therapeutics and ZoBio initiated a collaboration to develop small-molecule inhibitors of the “writer” protein complex METTL3/METTL14, a SAM-dependent methyltransferase that modifies mRNA encoded adenosine in the messenger RNA to m6A and thereby regulates protein expression. Through extensive protein engineering, multiple forms of the complex have been generated that enable all of the planned studies. Using Surface Plasmon Resonance to screen ZoBio’s diverse fragment library, the collaboration has resulted in the discovery and validation of multiple, drug-like substances that selectively modulate the function of the METTL3/METTL14 complex and have the potential to be optimized towards pre-clinical candidates. ZoBio’s unique expertise in both Nuclear Magnetic Resonance spectroscopy and protein crystallography has enabled the deep understanding of the mode of action of these chemotypes at atomic resolution. With our combined arsenal of capabilities and expertise, Gotham Therapeutics and ZoBio are well positioned to generate in vitro and in vivo active inhibitors that will further Gotham’s programs and the field of epitranscriptomics.