Online Focused on discovery and optimization challenges of small molecule drug candidates, Drug Discovery Chemistry is a dynamic virtual event for medicinal and biophysical chemists working in pharma and biotech. Gregg Siegal has presented the lecture: ‘Biophysics-Based Drug Discovery for Epitranscriptomics‘ during Fragment-Based Drug Discovery session. Afterwards, together with other speakers he participated in interesting…
Axxam and ZoBio Form a Strategic Alliance Integrating their Drug Discovery Services Platforms
MILAN, IT, AND LEIDEN, NL
Axxam and ZoBio have initiated a strategic alliance to provide a combination of integrated discovery services spanning all phases from gene to fully optimized leads.
This alliance provides access to a synergistic, industry-leading…
YTHDF2 – An unprecedented epitranscriptomic reader protein
Challenge
Our client tasked us with setting up a complete “gene to lead” fragment-based drug discovery campaign.
Since the entire family is unprecedented, there were no “tool compounds” typically required to set up assays. As we progressed, further challenges presented themselves.
Achievements
By capitalizing on our unique expertise in developing customized biophysical assays, we created a biologically relevant compound screening cascade in the absence of tool compounds. The cascade delivered chemically diverse sets of validated fragments that we successfully elaborated towards lead compounds using structural information that could only be gleaned through NMR.
Mettl3/Mettl14 – An epitranscriptomic writer complex
Challenge
Mettl3/Mettl14 is a large (90 kDa) heterodimeric “writer” complex that uses S-adenosyl methionine (SAM) as a cofactor. Identifying low affinity, validated fragment hits in the large amount of electron density derived from X-ray diffraction data was extremely difficult.
Achievements
We developed a highly efficient structure pipeline capable of determining up to 10 sub 2Å structures per month which has been the basis for elaborating fragment hits to cellular activity and beyond. Multiple chemotypes are promising, allowing for a robust hit-to-lead campaign.