Cresset Discovery has delivered a highly efficient digital workflow combining their molecular modeling expertise with Cresset technology to accelerate discovery, design and optimization of a METTL3 inhibitor. Working with Epics Therapeutics, the workflow combines scaffold hopping, in silico design and prioritization together with Epic’s medicinal chemistry team to drive efficient hit discovery and optimization, enabling progression towards a drug development candidate.

The work, published in a recent paper, and summarized in this article, demonstrates the application of Cresset’s unique technology to analyze the 3D shape and electrostatic environment of ligand-protein interactions and the further use of this signature to discover, design and optimize hit molecules. This computational analysis was applied within an effective workflow that furnished and prioritized new designs, informed by iterations of biological testing by Epics, to accelerate selection of an in vivo proof of concept compound.

Dr Martin Slater, Director of Discovery and co-author on the paper said:

“We are delighted to have worked on this project with the talented team of scientists at Epics Therapeutics, demonstrating the power of combining computational methods with expert medicinal chemistry, providing significant efficiency gains through the hit identification and optimization phases of a drug discovery project.”

With thanks to Epics Therapeutics for their kind acknowledgement in the paper:

“We are grateful to Dr. Slater and his team at Cresset Discovery, UK for the exceptional modeling work conducted.”