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As a leading service supplier in antibody-drug conjugate (ADC) development, BOC Sciences provides flexible ADC linkers product suite and bioconjugation service at competitive prices. We provide various ADC linkers development services for global customers to achieve new drug discovery milestones with comprehensive and advanced platforms.
With the improvements in payloads, linkers and conjugation methods, the development of antibody conjugated drugs (ADC) has achieved significant progress during the past decade. In particular, linker design plays a crucial role in regulating the stability of ADC in systemic circulation and payload release efficiency within tumors, thereby affecting the pharmacokinetics (PK), efficacy and toxicity characteristics of ADCs. Currently, two types of linkers are used according to different mechanisms, and they are cleavable linkers and non-cleavable linkers.
Key ADC linker parameters, such as conjugation chemistry, linker length, and linker steric hindrance, affect the PK and efficacy of ADC drugs. Therefore, in the design of ADC drugs, BOC Sciences provides customized services that support the correct adjustment of essential linker parameters to balance the stability and payload release efficiency, thus achieving suitable and successful ADC drugs developments.
ADC undergoes biotransformation in the systemic circulation and tissue cells. In addition to antibody metabolism and catabolism, linker deconjugation, linker degradation, and payload metabolism are considered typical biotransformation pathways. Ideally, ADC drug design seeks to remain intact and stable in the circulation before reaching the target cell. BOC Sciences provides comprehensive solutions involving conjugation site selection and linker modification to enhance ADC stability, such as adjusting conjugation sites point, linker length and linker steric hindrance.
Binding sites can also become affecting factors in payload release kinetics. Generally, binding sites directly affect release kinetics independent of the monoclonal antibody. Moreover, the introduction of sterically hindered chemical modification at the cleavage site can regulate ADC stability, thus leading to delay or ineffective release of the payload.
In order to obtain the most suitable ADC drug, linker design and integration are necessary. Linker integrated design includes multiple parameters, such as conjugation site, linker length, linker chemistry, cleavable/non-cleavable linkage, and steric hindrance of the proximal linkage. BOC Sciences provides optimized linker design schemes to balance ADC stability and payload release kinetics so that the release of the payload within tumor cells reaches a higher therapeutic threshold.
Higher ADC doses do not always improve drug efficacy. In fact, once a critical threshold is reached, an increase in dosage may lead to potential toxicity. Therefore, it is necessary to integrate linker and dose designs thus discovering the minimum effective dosage. When single-dose and multiple-dose regimens reveal similar effects, BOC Sciences is capable of helping our customers to choose the most suitable dosage that achieves the best curative effect and minimal toxicity.
The breakage of linkers directly controls cytotoxic molecules release. In order to reduce the off-target toxicity of ADC, it is necessary to design selective break sites. BOC Sciences can provide global customers with support services at the following break sites: histone enzymolysis sites, acidolysis sites, GSH cleavage sites, divalent iron cleavage sites, novel enzymatic sites, photosensitive sites, and non-cleavable linkers.
Currently, the connection between linker and antibody confront two major obstacles, reverse Michael addition reaction of the maleimide linker and uneven DAR value. In order to solve the first problem, BOC Sciences adopts various substituents to achieve upregulated stability while maintaining the high reactivity and specificity of maleimide linkers.
The connection between linker and payload is minimal, and the most common ones are amide bonds and ester bonds. As payload structures become more diversified, the restricted connection mode limits their connections with linkers. BOC Sciences develops linkers that adapt to diversified payloads, so as payloads that suit existing linkers.
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