termsTerm
DXd
aka MAAA-1181a, deruxtecan payload, MAAA-1181a, exatecan derivative
DXd is the topoisomerase poison inside Enhertu and Dato-DXd: about ten times stronger than SN-38, it spreads to neighbouring cells and leaves the body quickly once released.
DXd is a derivative of exatecan. Its potency allows a drug-to-antibody ratio of eight while remaining tolerable, and because the free payload crosses membranes it kills nearby cells that lack the target (the bystander effect), which is why Enhertu works in HER2-low disease. Its short half-life once released limits systemic exposure. Interstitial lung disease is the characteristic toxicity of the DXd platform. It is a partial substrate for efflux pumps, so payload resistance can be shared with other topoisomerase-I ADCs.
Category
ADC chemistry