Sygnature Discovery and UBE Corporation successfully identify potent SHP2 degrader compounds

Sygnature Discovery identifies potent SHP2 degrader compounds using its proprietary targeted protein degrader platform, CHARMED, in collaboration with Japanese specialty chemical company, UBE Corporation.


Sygnature Discovery and UBE Corporation have begun a collaboration on a hit-to-lead program to identify SHP2 degraders. SHP2 is a tyrosine-specific phosphatase implicated in human cancers and the objective is to develop potent bifunctional compounds with excellent ADME and PK properties for efficient degradation of SHP2.

Through the collaboration, the teams have discovered unique hit compounds (profile: single-digit nM DC50 and approximately 100% Dmax) utilising Sygnature Discovery’s innovative proprietary CHARMED technology platform.

The CHARMED platform was developed by Sygnature Discovery to deliver rapid synthesis, screening, and characterization of bifunctional lead compounds. To achieve this, CHARMED utilizes ready-to-couple plates of diverse linkers and popular ligase warheads in combination with high throughput biology approaches, accelerating identification of degrader hits for novel targets.

Bifunctional degraders function via induced proximity to a ubiquitin-ligase, relying on access to compounds that bind the target of interest. These can be identified via affinity-based methods such as FBDD, ASMS or DEL screens and used in CHARMED to rapidly assess activity of degrader compounds for novel targets.

Simon Hirst, CEO of Sygnature Discovery says:

“The physical properties of targeted protein degradation and bifunctional molecules are unusual compared to classical small molecule development, as they’re outside the rule of five. We therefore need technologies that assess these properties and filter them to allow selection of the best druggable molecules. There’s a lot of interest in targeted protein degradation and bifunctional molecules of this type but a lot of people are struggling to find start points in the programs or to find molecules that have the right properties to succeed in the clinic.

“We’re delighted to support the work of UBE Corporation. Our CHARMED platform brings together high throughput chemistry capabilities with high throughput biology, so we’re supporting the rapid synthesis of bifunctional molecules with a series of assays and platforms that will assess their potential to go forward.”


About Sygnature Discovery

Sygnature Discovery is a world-leading integrated drug discovery Contract Research Organisation based in the UK and Canada with its headquarters in Nottingham and additional sites in Alderley Park, Macclesfield, Glasgow, Montreal and Quebec City. Its staff of over 1,000 employees, which includes more than 900 scientists, partners with global pharma, biotech and NFP organisations.

Since 2011, Sygnature Discovery has delivered over 40 novel pre-clinical and 22 clinical compounds, with its scientists named on over 170 patents. Therapeutic areas of expertise include oncology, inflammation and immunology, neuroscience, metabolic diseases, infectious diseases, fibrotic diseases and more.


About UBE Corporation

UBE Corporation encompasses a group of specialty chemicals businesses, of which the pharmaceuticals business comprises the core of its life sciences portfolio, progressing beyond its track record of discoveries in small molecule therapeutics into high added-value products such as ADCs (antibody-drug conjugates) and bifunctional degraders. Alongside is a CDMO (contract development and manufacturing organization) business, which is strengthening its existing small molecule production capacity while also acquiring capabilities in novel modalities such as oligonucleotide therapeutics.  UBE Corporation’s life science businesses will continue to offer solutions that enhance and protect human life and health.

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