Another possible modification is to insert a methylene between hydroxyl and lactone on the E-ring yielding a seven membered β-hydroxylactone group, so-called homocamptothecin (hCPT). The hCPT’s hydroxyl has less inductive effect on the carboxyl group which makes the lactone very reactive. This enhances the interaction of the free hydroxyl group optimally with topo I and the covalent complex that forms in its presence are more stable. The E-ring of hCPT opens more slowly and the opening is irreversible . hCPTs exhibit enhanced human plasma stability because of decreased protein binding and more affinity for red blood cells than CPT.