Small molecule-induced protein degradation is an attractive strategy for the development of chemical probes. Protein degraders have the power to abrogate all of the functions of a drug target at once, including scaffolding functions which are difficult to target with small molecule inhibitors. A novel class of PROTACs that incorporate small molecule VHL ligands to successfully degrade HaloTag7 fusion proteins is developed. HaloPROTACs will inspire the development of future PROTACs with more drug-like properties. In HEK 293 cells stably expressing GFP-HaloTag7, 24 hour treatment with HaloPROTAC1 leads to less than 20% degradation, the longer HaloPROTAC2 leads to nearly 70% degradation of GFP-Halotag7 at 2.5 μM. HaloPROTACs containing protein degrader 1 leads to nearly 70% degradation of GFP-HaloTag7, when sufficiently long linkers are used. Derivative of the von Hippel-Lindau (VHL) ligand, VH 032, commonly used as a precursor to PROTACs that hijack VHL as the E3 ubiquitin ligase component. Supplied with a primary amine functional handle at a position known not to significantly affect binding to VHL, for ready conjugation to a linker/target protein ligand.
Functionalized VHL ligand for PROTACs
CAS No. 1448189-80-7
Physical State: Lyophilized white powder
Quantity: 5 mg; 10 mg; 25 mg
Solubility: 40 mg/mL in DMSO
Storage: Store desiccated as supplied at -20°C for up to 3 years. Store solutions at -80°C for up to 6 months or -20°C for up to 1 month.
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