SN-38

SN-38 blocks topoisomerase I, the enzyme that relieves twisting in DNA during copying, so the copying machinery collides with trapped complexes and the DNA breaks. It is about a thousand times more potent than irinotecan itself but only nanomolar, which is why sacituzumab govitecan carries roughly eight copies per antibody and uses a linker that lets go in the tumour environment. It is pumped out by the ABCG2 transporter, one route to resistance, and people who metabolise it slowly (UGT1A1*28) get more diarrhoea and low blood counts.