CRBN-Recruiting Bcl-xL/Bcl-2 Dual Degraders
Novel PROTACs designed to reduce platelet toxicity Potency increased 10x from previous generation
METTL3/METTL14 Degraders
The bifunctional molecules are optimized to bind both METTL3/METTL14 and a ubiquitin E3 ligase (e.g., VHL and CRBN), recruiting the E3 ligase to the vicinity of METTL3/METTL14 for polyubiquitination and subsequent proteasomal degradation. PROV filed 1-2024
Bifunctional TEAD Degraders
A series of bifunctional TEAD Degraders (PROTACs) PROV filed 1-2024
YAP-TEAD – Covalent Inhibitors Targeting Lipid Binding Pocket of TEAD
YAP and TEAD2 are prognostic factors for hepatocellular carcinoma Two chemical scaffolds; lead compound identified Xenograft data (Huh7)
PRMT5 Inhibitors Targeting MTAP Deleted Cancers
PRMT5 symmetrically di-methylates arginine residues and is overexpressed in tumors PRMT5 inhibition is effective in MTAP deleted cancers due to increased MTA concentrations, which sensitize the MTAP -/- cells to inhibition PRMT5 inhibitors need to work cooperatively with MTA Two targets identified with triple negative breast cancer
HDAC8 Degraders
Selective PROTAC degraders of histone deacetylase 8, not dependent on co-factors for enzymatic activity
Gatorbulin Analogues
Analogues of a natural product that affect tubulin polymerization and have anti-proliferative activity Better solubility than paclitaxel