Camptothecin, derived from a Chinese ornamental tree, inhibits topoisomerase I, an enzyme that allows DNA unwinding. Despite showing promise in preclinical studies, the agent had little antitumour activity in early clinical trials, and dosing was limited by kidney toxicity: its lactone ring is unstable at neutral pH, so while in the acidic environment of the kidneys it becomes active, damaging the renal tubules. In 1996 a more stable analogue, irinotecan, won Food and Drug Administration (FDA) approval for the treatment of colon cancer.