As the world's leading ADCs supplier, BOC Sciences focuses on the development and large-scale production of customized ADCs cytotoxins, linkers, and cytotoxins-linkers conjugates. We have the leading synthesis and production technology of ADC products that can well control the stability of ADCs, simplify the antibody screening process, and greatly shorten product development steps, which helps to reduce the production cost of such drugs.
SN-38 (7-ethyl-10-hydroxy-camptothecin), an active metabolite of irinotecan, has been demonstrated to have a broad spectrum of activity against mammalian cancer cells including NSCLC cells, small-cell lung cancer cells, and colorectal cancer cells. SN-38 prevents the religation of breaks in single-DNA strands by stabilizing the strands in a DNA-topoisomerase I (topo I) cleavable complex. SN-38 induces DNA damage and transient S-phase arrest, and these interactions have lasting effects that are correlated with its cytotoxic activity. Topo I activity is important for the initiation and elongation during DNA synthesis. It has been found that the topo I expression level and activity are positively correlated with the cytotoxicity of topo I inhibitors both in vitro and in vivo. Currently, SN-38 has been widely used in the research and development of antitumor drugs. For example, Trodelvy® is an ADC drug for the treatment of triple-negative breast cancer. Mechanistically, Trodelvy® binds to the TROP-2 receptor and enters the cells. Then, the payload SN-38 is released by linker hydrolysis, and prevents the re-connection of single strand breaks induced by topoisomerase I.
Fig. 1. Structural of Trodelvy® (MAbs. 2021, 13(1): 1951427).
As a professional ADC technology development platform, BOC Sciences provides customized design of linkers based on specific payloads to improve the stability of ADC conjugation intermediates or finished products by adjusting the length and steric hindrance of linkers. Our ADC technology platform also supports linker integrated design for optimal efficacy. In addition to acid cleavable linkers that have been applied to ADCs, we also offer other universal linkers screening and custom development services for SN-38 cytotoxins, such as disulfide linkers, amide linkers, thioether linkers, and enzyme cleavage linkers.
Currently, the global ADC drug development is mainly concentrated in the tumor field, of which solid tumors are the most popular and most of them are mature targets. With the progress of antibody screening and genetic engineering technology, the specificity and stability of ADC drugs have been enhanced, thereby improving the safety factor. Additionally, the indications of ADC drugs have gradually developed from tumor to other diseases, such as infection, autoimmune and metabolic diseases. From the perspective of target layout, the current ADC drugs development focuses on mature targets, mainly of those have been marketed ADC drugs or have been verified in other therapies. As a leading comprehensive ADC development and manufacturing service provider, BOC Sciences provides professional technical support for our clients to explore innovative targets and facilitates them to develop target tracks with obvious competitive patterns. Our ADC target development customized services include:
In addition to the linker length and steric hindrance, the conjugation site and steric hindrance of antibody are also important for the ADC drugs stability. The conjugation method will directly affect the quality of ADCs, thereby regulating the safety and efficacy of ADC products. With our state-of-the-art equipment and extensive R&D expertise, BOC Sciences can provide custom antibody modification and conjugation technologies with high specificity and affinity for specific cytotoxin-linker conjugates with short turnaround times.
A team of highly skilled experts from BOC Sciences designs and synthesizes various SN-38 derivatives and linkers according to specific project requirements. These linkers may be pH-sensitive, cleaved by specific enzymes, or triggered by other stimuli present in the target environment. By carefully considering the physicochemical properties of the linker, BOC Sciences ensures the successful synthesis of stable and biocompatible drug conjugates while maintaining cytotoxic activity.