Five More E3 Ubiquitin Ligases Added to Glue Platform
Vipergen’s cell-based molecular glue screening platform now covers 30 ready-to-use E3 ubiquitin ligases, following the addition of GID4, KLHDC2, NEDD4L, RNF126 and ZER1.
Degraders reported to date recruit a very limited number of ligases, the most frequent being CRBN or VHL – a fraction of the >600 human E3 ubiquitin ligases. That reliance narrows which targets can be degraded, offers little tissue selectivity and leaves programmes in crowded IP space. Expanding the ligase toolbox is therefore a priority in targeted protein degradation.
The newly incorporated ligases broaden the structural diversity of the panel:
GID4, the substrate receptor of the CTLH complex (RING-type), recognizes N-terminal proline degrons, a mode entirely distinct from CRBN and VHL. GID4 also displays ligand-induced conformational plasticity allowing for accommodation of chemically diverse binders.
KLHDC2 is a substrate receptor of the CRL complex (RING-type) that recognizes C-terminal diglycine degrons and is well-validated as an alternative for degrader design. Published work has demonstrated KLHDC2 paralog-specific targeted protein degradation.
NEDD4L is a HECT-type ligase that forms a bond directly with ubiquitin before its transfer, a mechanism different from the RING-type ligases used in nearly all degraders to date.
RNF126 is a single-subunit RING-type ligase involved in cancer. Its structural and functional characterization is well established, and it has been engaged in rational design of molecular glue degraders.
ZER1 is also a substrate receptor of the CLR complex (RING-type) that recognizes N-terminal glycine degrons and is involved in quality control of protein N-myristoylation.
In addition to the panel, Vipergen offers tailored solutions, enabling rapid incorporation of new E3 ligases into its screening platform. The expanded panel reflects Vipergen’s continued investment in degrader discovery and in the technologies that make hard targets tractable.
About Vipergen ApS
Vipergen is a world-leading provider of small-molecule drug discovery services based on DNA-encoded library (DEL) technologies and is the first and only company capable of screening DELs inside a living cell. Vipergen provides its proprietary suite of leading-edge DEL technologies through funded discovery partnerships with leading pharmaceutical and biotechnology companies, including top pharmaceutical companies in the USA, EU, and Japan. For more details about Vipergen and the YoctoReactor® (yR), Binder Trap Enrichment® (BTE), and Cellular Binder Trap Enrichment® (cBTE) drug discovery technology platforms, please visit https://www.vipergen.com.
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