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What Is PROTAC Technology?

PROTAC (proteolysis-targeting chimeras) technology is a new approach to drug development that targets specific disease-causing proteins for degradation through the cell's own protein disposal machinery, rather than just inhibiting them. PROTAC molecules usually consist of three parts: ligand for the target protein, linker, and ligand for the E3 ligase. Once the target protein is ubiquitin-tagged, it is broken down into its amino acid components by the cell's proteasome machinery. This approach has the potential to overcome some of the limitations of traditional pharmacology, such as incomplete target inhibition and drug resistance.

Overview of the steps taken by PROTACs to degrade the entire target protein.Overview of the steps taken by PROTACs to degrade the entire target protein.[1]

What We Do in PROTAC Molecular Synthesis

Designing and synthesizing potent PROTAC molecules can be a challenging and time-consuming process. Combining powerful computer-aided drug design (CADD) capabilities and automated synthesis platforms, Alfa Chemistry is committed to providing efficient PROTAC molecular design and synthesis solutions to save customers a lot of testing time and capital costs.

  • Computer Aided PROTAC Molecular Design

At Alfa Chemistry, our in-house team of computational chemistry experts and medicinal chemists use advanced software and techniques to design and optimize PROTAC molecules based on the properties and therapeutic requirements of the target protein. Our computer-aided PROTAC molecular design services include, but are not limited to:

  • Discovery of PROTAC molecules by molecular docking and virtual screening.
  • Accelerating PROTAC molecular design through deep learning, molecular simulation and molecular dynamics simulation.
  • Optimize the properties of linker (including chemical properties, structure, length, hydrophilicity and rigidity, etc.) to improve the degradation efficiency of the target protein.
  • Predicting the pharmacokinetic and toxicity profiles of design molecules.

Docking research of PROTAC molecules by modeling tools.Docking research of PROTAC molecules by modeling tools. [2]

  • Automated PROTAC Molecular Synthesis

Relying on our automated synthesis platform, Alfa Chemistry can quickly synthesize a variety of different types of PROTAC molecules according to customer needs. Our team has extensive experience with PROTAC molecules, especially "click chemistry" reactions. In addition, our synthetic library is stocked with various types of synthetic reagents, PROTAC linkers, and E3 ligase ligands, to quickly respond to synthetic needs.

Typical E3 ligase ligands and PROTAC linkersTypical E3 ligase ligands and PROTAC linkers

Choose Alfa Chemistry

In Alfa Chemistry, experienced synthetic chemists and 7×24-hour automated synthesis workstations provide a strong guarantee for our high-quality, standardized, and efficient delivery of projects. In particular, computer-aided design allows the development of PROTACs against targets that may be challenging using traditional small molecule drugs, thus expanding the range of potential targets for drug discovery. To get started with our services, or to discuss our capabilities with a member of our expert team, contact us today.

References

  • Hongying Gao, et al. ACS Med. Chem. Lett., 2020, 11, 3, 237-240.
  • Jia Wu, et al. Acta Materia Medica., 2023. 2, 1, 42-53.
  • Shuangjia Zheng, et al. Nature Machine Intelligence, 2022, 4, 739-748.

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