KS119

KS119 is a small molecule hypoxia-activated prodrug (HAP) designed to selectively target oxygen-deficient regions within solid tumors. Developed at Yale University in the laboratory of Dr. Alan Sartorelli and licensed to Vion Pharmaceuticals, the compound is a sulfonylhydrazine derivative consisting of a nitrobenzyl trigger, an oxycarbonyl linker, and a cytotoxic 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)hydrazine (90CE) warhead. In the hypoxic tumor microenvironment, enzymatic nitroreduction of the nitrobenzyl moiety triggers the release of 90CE. This active species subsequently generates alkylating intermediates that produce DNA interstrand cross-links, leading to apoptosis. This selective activation mechanism is intended to provide a high therapeutic index by concentrating DNA-damaging activity within the tumor microenvironment while sparing well-oxygenated healthy tissues. Development of the compound was halted following the bankruptcy and liquidation of Vion Pharmaceuticals.

Other names

1,2-bis(methylsulfonyl)-1-(2-chloroethyl)-2-[[1-(4-nitrophenyl)ethoxy]carbonyl]hydrazine