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CL2A

CL2A is the deliberately fragile linker in Trodelvy: it releases SN-38 in the acidic tumour environment as well as inside cells, feeding the bystander effect.

CL2A is a pH-sensitive, hydrolysable linker with a short polyethylene glycol spacer. It releases roughly half its payload within a day in plasma, which would be a flaw for a more potent payload but suits moderately potent SN-38 at a very high drug-to-antibody ratio. The result is payload release both inside targeted cells and in the tumour microenvironment.

Category
ADC chemistry

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