- Science
- First-in-class oncology medicines targeting human kinome.
CHANDEL (CHAperoNe Mediated DEgrader pLatform) Technology
MBT scientific platform technology, termed as CHANDEL (CHAaperoNe Mediated DEgrader pLatform), is the key driver of our leading approach to target protein degradation (TPD). Utilizing our CHANDEL technology, we can efficiently identify new chaperon degradable disease-causing molecular targets by a collection of experimental approaches and key elements that provide us with the ability of design, analyze and evaluate degrader performance.
We made a significant investment in collection of diverse sets of HSP90 inhibitors (pan-HSP90 inhibitors, HSP90a,b selective inhibitors, HSP90b selective inhibitor and C-terminal domain HSP90 inhibitors) and in-house synthesized DMPK favorable linkers (>200). Computer-based tools allow us to design degrader exit locations to connect HSP90 binder and POI by linker technology and enhanced potency and selectivity. Most of our discovery projects, we use cell-based assays as a primary assay that measure degradation of disease-causing targets to evaluate degrader performance These data are critical to answer two key questions that are important in the NO/GO decision tree.
How does chaperon degrader selectivity over HSP90 binder itself and combination with warhead? 2) targeting for POI? 3) How fast does the chaperon degrader remove target protein and how much target protein remains in cells after treatment of degrader. As the progress of degrader development, we do have a system to evaluate chaperon degrader MoA such as ternary complex formation assay, FRET assay, ubiquitination assay and target engagement assay to in vivo efficacy study.
Taking CHANDEL technology, we developed the first-in-class orally available mtPI3K chaperon mediated degrader without causing dose limited toxicity such as hyperglycemia and several early lead stage programs are actively under progressing.
We made a significant investment in collection of diverse sets of HSP90 inhibitors (pan-HSP90 inhibitors, HSP90a,b selective inhibitors, HSP90b selective inhibitor and C-terminal domain HSP90 inhibitors) and in-house synthesized DMPK favorable linkers (>200). Computer-based tools allow us to design degrader exit locations to connect HSP90 binder and POI by linker technology and enhanced potency and selectivity. Most of our discovery projects, we use cell-based assays as a primary assay that measure degradation of disease-causing targets to evaluate degrader performance These data are critical to answer two key questions that are important in the NO/GO decision tree.
How does chaperon degrader selectivity over HSP90 binder itself and combination with warhead? 2) targeting for POI? 3) How fast does the chaperon degrader remove target protein and how much target protein remains in cells after treatment of degrader. As the progress of degrader development, we do have a system to evaluate chaperon degrader MoA such as ternary complex formation assay, FRET assay, ubiquitination assay and target engagement assay to in vivo efficacy study.
Taking CHANDEL technology, we developed the first-in-class orally available mtPI3K chaperon mediated degrader without causing dose limited toxicity such as hyperglycemia and several early lead stage programs are actively under progressing.
