Deruxtecan-based Linker and Cytotoxin Conjugation

Deruxtecan-based Linker and Cytotoxin Conjugation

Deruxtecan-based Linker and Cytotoxin Conjugation

BOC Sciences has built a world-leading coupling technology platform. We can combine the research of complex, highly active small molecules and antibodies through our platform. Nowadays, we have accumulated rich research data and practical project experience in the interaction of targets and antibodies, continuously optimize coupling technology and production capacity, and provide an integrated ADC coupling technology platform from early research and development to GMP production.

Introduction

Deruxtecan (DXd) payloads are potent topoisomerase I inhibitors targeting HER2. Currently, deruxtecan-based drugs are widely studied for the treatment of various diseases, such as lung, rectal, gastric, breast, and uterine cancers, etc. For example, trastuzumab deruxtecan (Enhertu®), an antibody-drug conjugate (ADC) drug, was approved by the FDA in December 2019 for the treatment of HER2-positive breast cancer. Enhertu® is a novel HER2-targeted drug featuring humanized anti-HER2 antibody linked to the topoisomerase I inhibitor payload (DXd) via a cleavable tetrapeptide linker. After internalization, the linker is cleaved by lysosomal enzymes to release the payload and cause DNA damage, leading to apoptosis.

 Structural of trastuzumab deruxtecan (MAbs. 2021, 13(1): 1951427). Fig. 1. Structural of trastuzumab deruxtecan (MAbs. 2021, 13(1): 1951427).

Our Services

Linkers Screening and Design For Deruxtecan Cytotoxins

Ideally, ADCs are designed to maintain integrity and stability in the circulation before entering target cells. BOC Sciences has developed a number of approaches involving coupling site selection and linker modification to enhance ADC stability. Typically, we can modify each component for this purpose, including antibodies, linkers, and payloads. Our scientists can tune-up key linker parameters such as coupling chemical site, linker length, and linker steric hindrance for specific payloads (such as deruxtecan) to achieve a balance between ADC stability and payload release efficiency.

Targets Screening For Deruxtecan-Linker Conjugates

In addition to providing target screening services for cytotoxin-linker intermediates, our scientists are dedicated to providing cytotoxin development, linker development and cytotoxin-linker coupling process optimization services. Empowered by our advanced platforms and experienced technical personnel, our one-stop platform focuses on custom development services for the following targets: HER2, MSLN, CD19, CD33, CD30, CD22, CD79B, Nectin-4, BCMA, TROP-2, EGFR, TF, etc. Additionally, BOC Sciences is fully competent to serve as your one-stop-shop for ADC development against various cancer. Our disease research services including:

Deruxtecan-based Linker and Cytotoxin Conjugation

Antibodies Screening and Modification For Deruxtecan-Linker Conjugates

As a large chemical service organization, BOC Sciences is dedicated to providing antibody screening and modification services for ADC drug development programs. We always adhere to the antibody screening principles of high specificity, high affinity, low immunogenicity and low cross-reactivity. With years of experience in antibody modification, BOC Sciences will screen and design the most suitable antibody based on the type, length and steric hindrance of the payloads and linker conjugates. Now BOC Sciences offers a fully integrated service for the development of ADCs with first-class conjugation strategies and technology platforms.

Deruxtecan-based Linker and Cytotoxin Conjugation1

References

  1. Kotschy, A. et al. The Chemistry Behind ADCs. Pharmaceuticals (Basel). 2021, 14(5): 422.
  2. Zhang, G. et al. Linkers Having a Crucial Role in Antibody-Drug Conjugate. Int. J. Mol. Sci. 2016, 17: 561.
  3. Tsuchikama, K. et al. Antibody-drug conjugates: recent advances in conjugation and linker chemistries. Protein Cell. 2018, 9: 33-46.
  4. Zhang, B. et al. Targeting cancer with antibody-drug conjugates: Promises and challenges. MAbs. 2021, 13(1): 1951427.
* Only for research. Not suitable for any diagnostic or therapeutic use.

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