Ubiquitin Specific Protease Platform

Target Class

Deubiquitinase (DUB) / Ubiquitin Specific Protease (USP)

Modality

Small molecule

Descriptor

Innovative USP/DUBs drug discovery platform

Status

The platform is now being exploited for a number of DUBs.  Small molecule inhibitors and fragments have been identified and subsequently validated.  These provide new exciting opportunities for Medicinal Chemistry.  De novo target identification and validation efforts are also an integral part of this discovery platform to ensure sustainability and the development of truly innovative therapeutics.

A rare and exciting opportunity to create a whole new world of therapeutics

Targets in the ubiquitin-proteasome system have yielded only a few authorised drugs to date, the likes of Velcade®, Revlimid® and Kyprolis®, yet these drugs, despite severe limitations, have revolutionised the treatment of multiple myeloma. However, it is a disappointment  that yet more clinical benefit has not been realised outside multiple myeloma and that, even within the indication, poor selectivity and toxicity limit their use.

Ubiquitin Specific Proteases (USPs) act north of the proteasome and exhibit exquisite control of protein degradation and signalling. As yet they have proved difficult to drug by conventional means although they hold out the promise of lower toxicity and access to a wider range of indications. In particular, we believe there is a chance that greater efficacy and treatment of solid tumours can be realised. Ubiquitin Specific Proteases (USPs) have proven to be particularly difficult to target with small molecules over the past decade, however, we at Almac Discovery are committed to change that.

Recognising the unique therapeutic potential of the ubiquitin-proteasome system, Almac Discovery has developed a purpose-built, fully comprehensive assay and hit finding platform (Ubi-PlexTM) with the aim of identifying and developing novel inhibitors for therapeutically relevant USPs.

Almac Discovery’s platform has identified low molecular weight binders of multiple USPs that are highly potent, selective and reversible inhibitors.