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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.
作为抗体药物偶联物 (ADC)开发领域的领先服务供应商， BOC Sciences以具有竞争力的价格提供灵活的ADC 连接器产品套件和生物偶联服务。我们为全球客户提供各种 ADC 连接器开发服务，通过全面、先进的平台实现新药发现的里程碑。
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.
随着有效负载、连接体和缀合方法的改进，抗体缀合药物（ADC）的开发在过去十年中取得了重大进展。特别是，接头设计在调节ADC在体循环中的稳定性和肿瘤内有效负载释放效率方面发挥着至关重要的作用，从而影响ADC的药代动力学（PK）、功效和毒性特征。目前，根据不同的机制使用两种类型的连接子，它们是可切割连接子和不可切割连接子。
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.
关键的 ADC 连接体参数，例如缀合化学、连接体长度和连接体空间位阻，会影响 ADC 药物的 PK 和功效。因此，在ADC药物的设计中，BOC Sciences提供定制服务，支持正确调整关键连接参数，以平衡稳定性和有效负载释放效率，从而实现合适且成功的ADC药物开发。
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.
ADC 在体循环和组织细胞中进行生物转化。除了抗体代谢和分解代谢之外，接头解离、接头降解和有效负载代谢被认为是典型的生物转化途径。理想情况下，ADC 药物设计力求在到达靶细胞之前在循环中保持完整和稳定。 BOC Sciences 提供涉及缀合位点选择和接头修饰的全面解决方案，以增强 ADC 稳定性，例如调整缀合位点、接头长度和接头空间位阻。
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.
结合位点也可能成为有效负载释放动力学的影响因素。一般来说，结合位点直接影响释放动力学，与单克隆抗体无关。此外，在裂解位点引入空间位阻化学修饰可以调节ADC稳定性，从而导致有效负载的延迟或无效释放。
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.
为了获得最合适的ADC药物，连接子的设计和集成是必要的。连接子集成设计包括多个参数，例如缀合位点、连接子长度、连接子化学、可裂解/不可裂解连接以及近端连接的空间位阻。 BOC Sciences 提供优化的连接器设计方案，以平衡 ADC 稳定性和有效负载释放动力学，从而使肿瘤细胞内有效负载的释放达到更高的治疗阈值。
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.
较高的 ADC 剂量并不总能提高药物疗效。事实上，一旦达到临界阈值，剂量的增加可能会导致潜在的毒性。因此，有必要将连接体和剂量设计结合起来，从而发现最小有效剂量。当单剂量和多剂量方案显示相似效果时，BOC Sciences能够帮助我们的客户选择最合适的剂量，以达到最佳疗效和最小毒性。
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.
连接体的断裂直接控制细胞毒性分子的释放。为了降低ADC的脱靶毒性，需要设计选择性断裂位点。 BOC Sciences可以为全球客户提供以下断裂位点的支持服务：组蛋白酶解位点、酸解位点、GSH裂解位点、二价铁裂解位点、新型酶位点、光敏位点和不可裂解连接子。
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.
目前，接头与抗体的连接面临两大障碍，马来酰亚胺接头的逆迈克尔加成反应和DAR值不均匀。为了解决第一个问题，BOC Sciences采用各种取代基来实现稳定性上调，同时保持马来酰亚胺连接体的高反应性和特异性。
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.
连接体和有效负载之间的连接很少，最常见的是酰胺键和酯键。随着有效负载结构变得更加多样化，受限连接模式限制了它们与链接器的连接。 BOC Sciences开发了适应多样化有效负载的连接器，从而成为适合现有连接器的有效负载。
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