ADC Linkers Development

ADC Linkers Development

BOC Sciences provides flexible ADC linker product suite and biocoupling service with competitive price. The antibody drug conjugate (ADC) is composed of ideal monoclonal antibodies, effective cytotoxic drugs and appropriate linkers. Linker is responsible for connecting cytotoxic load and McAb, and maintaining the stability of ADC in systemic circulation. The chemical properties and coupling sites of linker play an important role in the stability, pharmacokinetics, pharmacodynamics and therapeutic window of ADC.

At present, there are two types of linkers according to different mechanisms, the first is the cleavable linker, the second is the noncleavable linker. There are three different types of release mechanisms for cleavable linkers:

  • Lysosomal protease sensitive linkers. A lysosomal protease, such as cathepsin B, is used to recognize and cleave a dipeptide bond, thereby releasing the free drug from the conjugate.
  • Acid sensitive connector. The advantage of this kind of linker is to activate the hydrolysis of an acid unstable group in the linker to release the drug in the low pH environment of lysosome.
  • Glutathione-sensitive linkers. This strategy utilizes a higher concentration of mercaptan in the blood than in the cells, such as glutathione. The disulfide bonds in the linker are relatively stable in the blood circulation, but the glutathione is reduced in the cells to release the free drug.

The cleavable linker can be further divided into a small molecule linker and a macromolecular linker depending on the molecular size of the linker. ADCs coupled with small molecule linkers have poor water solubility and good water solubility of the antibody, which leads to large toxic side effects of protein aggregation.

Currently, BOC Sciences can provide the following linker tools

  • DBCO, tetrazine, BCN and cyclopropene
  • Biotin linker
  • PEG linker
  • Peptide linker
  • Glucuronide linker
  • Photolysis linker
  • Dye probe linker
  • Folic acid PEG linker

BOC Sciences's quality system ensures that the ADC production process conforms to the us FDA, EU EMA and China NMPA GMP standards.

GMP manufacturing capabilities

  • Synthesis of large-scale cytotoxins and linkers under GMP conditions
  • Precise control of the ADC coupling process in a GMP environment with complete QA/QC supervision
  • Mature linker and cytotoxic technology
  • Extensive experience in ADC conjugation and process amplification

Our advantages

  • True loyalty and partnership
  • Skilled chemistry team
  • Fully equipped analytical support
  • High quality, low cost products
  • Advanced technology and methods
  • Comprehensive analysis of biopharmaceutical services

References:

  1. Mark Frigerio & Andrew F. Kyle. The chemical design and synthesis of linkers used in antibody drug conjugates. Curr Top Med Chem. 2017;17(32):3393-3424.
  2. Jain, Nareshkumar, Smith, Sean, Ghone, Sanjeevani, & Tomczuk, Bruce. (2015). Current adc linker chemistry.Pharm Res. 2015;32(11):3526-40.
* Only for research. Not suitable for any diagnostic or therapeutic use.

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