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New E3 Ligase Mediated Protein Degrader
In addition to our core CHANDEL technology, we are dedicated to expanding the collection of new E3 ligase that can be taken advantage of TPD.
As a POC study, we used peptide ligands for Kelch-like homology domain-containing protein 2 (KLHDC2) and linked to JQ1 for BET-family neo-substrate recruitment. This is the first example of targeted kinase degradation by KLHDC2 ubiquitin E3 ligase and published paper in the Cell. Chem. Biology in 2023, we highlighted as follows;
1) A PROTAC that induces protein degradation via the KLHDC2 E3 ubiquitin ligase.
2) Pharmacological demonstration that KLHDC2 is suitable for targeted protein degradation.
3) KLHDC2-mediated target degradation at low-cellular target occupancy.
Main drawback of peptide based KLHDC2 E3 ligase binder is poor permeability and unfavorable drug-like properties. In order to overcome these issues, we have a second generation KLHDC2 program, small molecule KLHDC2 binder / di-Glycine prodrug approaches and we are currently preparing manuscript to disclose a small molecule ligand targeting KLHDC2’s di-Gly binding site and patent filing with >600 examples are also under processing
As a POC study, we used peptide ligands for Kelch-like homology domain-containing protein 2 (KLHDC2) and linked to JQ1 for BET-family neo-substrate recruitment. This is the first example of targeted kinase degradation by KLHDC2 ubiquitin E3 ligase and published paper in the Cell. Chem. Biology in 2023, we highlighted as follows;
1) A PROTAC that induces protein degradation via the KLHDC2 E3 ubiquitin ligase.
2) Pharmacological demonstration that KLHDC2 is suitable for targeted protein degradation.
3) KLHDC2-mediated target degradation at low-cellular target occupancy.
Main drawback of peptide based KLHDC2 E3 ligase binder is poor permeability and unfavorable drug-like properties. In order to overcome these issues, we have a second generation KLHDC2 program, small molecule KLHDC2 binder / di-Glycine prodrug approaches and we are currently preparing manuscript to disclose a small molecule ligand targeting KLHDC2’s di-Gly binding site and patent filing with >600 examples are also under processing
