DISCOVERY
A new discovery for the future of polyene therapy
Researchers at the University of Illinois discovered that amphotericin B acts like a sponge on cell membranes, extracting sterols that are essential for membrane integrity. This includes ergosterol in fungal cells (which evoke fungal killing) and cholesterol in human cells (which cause toxicities). This discovery enabled a model to create a polyene with greater specificity for fungal cells.
Rational drug design: Building a better polyene antifungal
The ‘sponge model’ informed two synthetic modifications: 1) epimerization of the mycosamine C2’ carbinol center, promoting extraction of ergosterol over cholesterol to systemic toxicities, and 2) replacement of the C16 carboxylic acid with a serinol amide, assisting antifungal activity. This work, exemplifying rational drug design at its best, ultimately led to Elion’s development candidate, EL219.
