Therapeutic Modalities
Targeted Protein Degradation
Axcelead Holistic Solution
for Targeted Protein Degradation (TPD) Drug Discovery
Axcelead has comprehensive capabilities in TPD drug discovery at the preclinical stages and a proven track record. No matter what stage your project is in, Axcelead will offer a tailored solution for you, whether you need support for part or all of it.
Targeted Protein Degradation
Targeted Protein Degradation (TPD) has emerged as a promising new therapeutic modality in drug discovery. Unlike traditional approaches that focus on inhibiting protein functions, TPD utilizes the ubiquitin-proteasome system to target specific proteins for degradation. In other words, it leverages the cell’s natural protein degradation machinery to selectively eliminate disease-causing proteins.
The Targeted Protein Degradation (TPD) offers many advantages, including:
- A broad target range, including previously undruggable targets
- More profound efficacy through the removal of the target protein
- Lower clinical doses due to its catalytic mechanism
- Improved safety through tissue or cell selective degradation
- Oral administration
TPD can be primarily classified into bifunctional degraders, such as PROTAC®, and monomeric degraders, including molecular glue degraders and monovalent degraders. Each type has its advantages and disadvantages. Bifunctional degraders can be designed rationally in initial discovery stage. On the other hand, the molecular complexity poses challenges of molecule optimization, synthesis, purification, ADME and so on. Regarding the discovery of monomeric degraders, in some cases, selectivity and identification of degradation mechanism are challenges. Another common hurdle of TPD is the need for a highly specialized and diverse assay system.
Axcelead Platform Solves Your Targeted
Protein Degradation Challenges
Bifunctional degraders
- Special chemistry accelerates hit generation, lead generation and candidate discovery.
Allow rapid access to an unprecedentedly diverse chemical space by using Axcelead’s degrader chemical toolbox, multi-step high-throughput synthesis and purification technologies.Identify promising bifunctional degraders more reliably and quickly. - Multiple technologies significantly increase the possibility of discovering bifunctional degraders with favorable ADME properties.
Expertized drug design know-how and ADME prediction technologiesADME evaluation technologies suitable for bifunctional degraders - Original POI binders against hundreds of drug targets
Over 500 targets’ binders are available at Axcelead, including many selective, unpublished compounds with desirable physiochemical properties for bifunctional degraders
Monomeric degraders
- Molecular glue degrader focused library improves the possibility to discover hit compounds with the presumed mechanism of degradation.
- Proteomics and proximity labeling technologies enable efficient discovery of the off-targets and novel neo-substrates.
- After discovery of hit compounds by phenotypic screening, Identification of degradation pathway and mechanism (CRISPR-cas9. Proximity labeling, IP etc.) is also available.
- We have dozens of original neo-substrate candidates. It could accelerate your project if your target of interest is included in candidates.
Protein Degraders Assay Capabilities
- Well-experienced and diverse high-throughput screening capabilities:
HiBiT®TR-FRETCell imaging assayNanoBRET®AlphaScreen*HiBiT® and NanoBRET® are registered trademarks of Promega corporation.
- Degrader validation assay
WBJESSDegradation pathway dependency - Degrader profiling assay
SPRProteomics - Many track records of E3 ligase preparation and screening
- X-ray crystallography