RxNfinity™ adapts the ‘virtual synthon’ approach first described by Sadybekov and colleagues in the leading science journal Nature in December 2021 (Nature volume 601, pages452–459 (2022)). “In effect the library is constructed in the active site of your target” says Nigel Ramsden, EVP at RxChemistry, who leads the medicinal chemistry group at RxCelerate. “Each building block in turn is assessed for quality of fit against the protein target, before being incorporated into the growing library, thereby tailoring the final chemical space to your target. It is conceptually simple, but the impact is transformative.”
The output from the computational phase is a collection of synthetically tractable drug-like molecules which can be readily made and tested. The whole process from target nomination to experimentally-verified hit takes about six weeks. Equally importantly, in times of geopolitical instability, all the experimental work can be completed in the United Kingdom using locally-sourced chemicals ensuring RxNfinity™ services are never disrupted.
“The key differentiation for RxNfinity™ is that the chemical space is dynamic, assembled de novo each time uniquely incorporating the structure of the particular target and using only tractable chemistry. This ensures the available library capacity is filled with better candidates, which translates to a higher chance of delivering more complex pharmacological profiles together with drug-like properties” explained Ramsden.
In addition to the designing and implementing the AI-based workflows, RxCelerate has made a large investment in state-of-the-art computing infrastructure to run the modelling. “We are also delighted to have signed an agreement with Newcastle University to access the ROCKET HPC service, as well as scalable cloud computing resources” said Heal “guaranteeing access to intensive processor power needed to deliver RxNfinity™ at scale.”
“This new concept of dynamic chemical spaces is transformative” said David Grainger, Executive Chairman at RxCelerate. “The ability to generate tractable bespoke libraries on the fly for each target is delivering better hits than even the largest static spaces. Better still, our vision is to make the very best technologies available to everyone on a fee-for-service basis, allowing anyone with a good idea to reduce it to practice. With RxNfinity™ small-molecule discovery just got easier.”