RxCelerate launches protein metastate discovery platform
RxCelerate, a leading international outsourced drug discovery and development provider, has launched RxPlorer™: a new technology for finding small molecule hits, particularly against challenging, previously undruggable targets.
RxPlorer™ explores the full folding landscape of a target to expose hidden, short-lived and cryptic pockets that do not appear in static crystal structures. By revealing these transient binding opportunities, RxPlorer™ provides clients with high value starting points for small molecule binders, allosteric inhibitors and monovalent degraders.
Developed by the computational scientists at ProsaRx, RxCelerate’s in silico design and discovery arm, RxPlorer™ uses a unique combination of methods: advanced molecular dynamics, steered accelerated dynamics, free energy calculations and machine learning informed docking of large chemical spaces. This approach allows the platform to search and characterise large, complex conformational landscapes and to prioritise pockets with the highest potential for ligand binding and downstream functional impact.
Dr Jill Reckless, CEO at RxCelerate, said:
RxPlorer is a transformational addition to our integrated discovery offering. As the only organisation offering metastate discovery as a service, RxCelerate is uniquely placed to take projects from discovery through hit validation and into lead optimisation with confidence and pace, maximising the value of the novel opportunities uncovered by RxPlorer.
Dr Jon Heal, EVP of ProsaRx at RxCelerate, said:
If a client brings us a protein with no obvious binding site, we can utilise RxPlorer rapidly and expect to be testing shortlisted small molecules within two months. The speed at which we can move from modelling to testing for difficult targets brings a new level of momentum to client programmes. Our rapid lead optimisation capabilities also continue through to candidate nomination, all delivered under one roof.
Studies in Eotaxin-1 (CCL11), a chemokine and key asthma target previously undrugged with small molecules, exemplify the capabilities of RxPlorer™. The team identified druggable metastates with binding pockets not visible in available static structures. Focused virtual screening against these states generated multiple classes of hits, which were experimentally verified, validating the biological relevance of the metastates uncovered.
RxPlorer™ is currently available to clients through an early adopter programme, one of which has recently shown high hit rates on an intracellular protein target. RxCelerate is inviting organisations seeking rapid discovery of novel hits for challenging targets to get in touch.
