AI Article Synopsis
- A new method has been developed to connect indole-containing drugs to antibodies using a carbamate linker and a special disulfide-based mechanism.
- This method was effectively used to attach a selective estrogen receptor down-regulator (SERD) to different antibodies, leading to strong, targeted reduction of estrogen receptor levels in specific cancer cells.
- The created drug-antibody combinations showed good stability in blood and maintained effectiveness when tested in mouse models with tumors.
Article Abstract
A novel strategy to attach indole-containing payloads to antibodies through a carbamate moiety and a self-immolating, disulfide-based linker is described. This new strategy was employed to connect a selective estrogen receptor down-regulator (SERD) to various antibodies in a site-selective manner. The resulting conjugates displayed potent, antigen-dependent down-regulation of estrogen receptor levels in MCF7-neo/HER2 and MCF7-hB7H4 cells. They also exhibited similar antigen-dependent modulation of the estrogen receptor in tumors when administered intravenously to mice bearing MCF7-neo/HER2 tumor xenografts. The indole-carbamate moiety present in the new linker was stable in whole blood from various species and also exhibited good in vivo stability properties in mice.
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| http://dx.doi.org/10.1002/chem.201800859 | DOI Listing |
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