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PROTAC-Related Custom Services

Introduction of PROTAC

PROTAC, short for PROteolysis-TArgeting Chimeras, is a heterobifunctional nanomolecule containing two different ligands, ligand for ubiquitin E3 and ligand for target protein. The two parts are connected by linker to form a "three-unit" polymer, target protein ligand-linker-E3 ligase ligand.

Once PROTAC molecule entering the cell, ligand for protein of interest (POI) can specifically bind to the corresponding target protein, while E3 ligase ligand can recruit E3 ligase to form the triadic complex of POI-Linker-E3 ligase, in which E3 ligase mediates ubiquitination on POI by ubiquitin from enzyme E2. POI labeled by ubiquitin is recognized and degraded by proteasome. It is not necessary for POI ligand to occupy the binding site for a long time during this progress because of instantaneous ubiquitination after short formation of the ternary complex, so PROTAC can be reused for many times in cell.

Elements of PROTAC

PROTAC molecules are generally composed of three parts: ligand for target protein, linker and ligand for E3 ligase.

Selection of ligand for E3 ligase(Ligand for E3 Ligase)

E3 ligase is a key structure for target protein ubiquitination. Its ligands include many types, among which CRBN (Cereblon), VHL (von Hippel-Lindau), IAP and MDM2 are now frequently used. Ligands of CRBN with good drug-likeness are generally preferred, followed by VHL and IAP derived from endogenous ligand peptides. Consideration should also be given to the abundance of the corresponding E3 ligase in the cell where the specific target protein is located and the physical and chemical parameters of the final PROTAC.

Selection of linker(PROTAC Linker)

Linkers are molecules that connnect ligand for E3 ligase and ligand for target protein. The properties of linkers have a great influence on the membrane permeability, efficacy and metabolic distribution of PROTAC. The ideal linker length should be able to maintain the lowest binding entropy of the two proteins without affecting their binding in space. There are also studies on multiple connectors and photoswitchable linkers.

Selection of ligand for target protein(Ligand for Target Protein for PROTAC)

As the guiding group of PROTAC, target protein ligand is responsible for capturing the target protein, which requires high coordination ability and selectivity. In practical applications, existing inhibitors and activators of proteins can be used as ligand candidates, while proteins without related molecule reports can be searched for ligands by high-throughput screening and Virtual Creening. It is not necessary for ligands to be inhibitor or agonist, but it should be highly specific to the target protein.

MedChemExpress Services

MedChemExpress (MCE) can provide one-stop services for the design, synthesis, analysis, purification, optimization, detection and evaluation of PROTAC-related products (Ligand for E3 Ligase、PROTAC Linker、Ligand for Target Protein for PROTAC、E3 Ligase Ligand-Linker Conjugate、Target Protein Ligand-Linker Conjugate、PROTAC、SNIPER、PROTAC-Linker Conjugate for PAC).

Our Advantages
  • Quick delivery

    Delivered for using at the earliest time, reducing the intermediate procedures

  • Price concessions

    High cost performance and competitive prices

  • Product reports

    Provide real and reliable experimental data related to PROTACs

  • In strict confidence

    Sign a confidentiality agreement
    with MedChemExpress (MCE) for absolute security

  • Professional consultation

    Professional technicians will answer and solve your doubts in time

  • Abundant species

    3,000+ PROTAC products
    for worldwide customers

  • Speciallized capacity

    Professional synthesis ability and
    rich experience

  • Cutting-edge technology

    Continuous technological innovation for
    design and synthesis service

Online Consulting

The corresponding scheme and price for PROTAC shall be determined after evaluation. For further information on service pricing or technical details, please email sales@MedChemExpress.com or contact MedChemExpress (MCE) sales staff directly.