Protac Synthesis

Protac Synthesis

We have extensive experience in the synthesis of Proteolysis Targeting Chimeras (PROTAC) and partial PROTAC for targeted protein degradation, including the development and functionalization of various E3-ligase ligands such as CRBN, VHL, MDM2 ,and cIAP1, some of them even in multi-gram scale. In addition to the synthesis of commercially available ligands, we are also experienced in developing novel structural analogues.

Our PROTAC synthesis and screening services for targeted protein degradation include:

• Synthetic capability to rapidly progress from milligram to gram scale and beyond
• Capability to develop novel linkers for discovery needs
• Experience in homo PROTACs and partial PROTACs and SNIPERs
• Capability of optimizing the NCEs for potency and better physicochemical properties
• In-house library of partial PROTACs and linkers for rapid target engagement
• Chemistry and integrated discovery support
• Stand-alone biology support including in vitro and in vivo profiling, DMPK, or toxicology

We also synthesize a large variety of linkers needed for the linkage of E3-Ligase ligands to the target-binding ligands, including PEG linkers, carbon-based chains, with a large variety of end functionalities including –NH₂, –CO₂H, –N₃, –C≡CH, –CHO, –X and –OH to be connected with almost any active targets.

We have unique capabilities for tailor-made partial PROTACs, which are ready for rapid target linkage. We also have a series of E3-ligase ligands and linkers on our shelves.
Our in-house collection offers clients a quick and efficient way to jump-start their drug discovery programs and reach meaningful conclusions faster.
We complement our medicinal chemistry of PROTACs with a vast experience in the biology of protein degraders and comprehensive in vitro biology support, including various biological assays, DMPK and toxicology support.

Our discovery biology expertise for PROTAC screening includes:

• TR-FRET assays for biochemistry (EnVision XCite)
• Cell-based assays for evaluating target degradation (Hi-Bit, Nano-Bit etc.) including calculation of DC50 values
• Preliminary ADME studies (e.g. permeability, solubility, microsomal stability)
• PK studies in rodents
• Xenograft studies and other PD models
• Toxicology studies
• Analysis of ternary complexes