Raltitrexed(ZD1694), an inhibitor of thymidylate synthase, is an antimetabolite drug used in cancer chemotherapy.

Raltitrexed (ZD1694) is a novel quinazoline folate analog that selectively inhibits thymidylate synthase. Intracellularly, raltitrexed is polyglutamated to its active form which can be retained in cells for prolonged periods. The clearance of raltitrexed ranged from 110 to 165 ml/min per m(2), and the steady-state volume of distribution exceeded 200 l/m(2). The CSF penetration of raltitrexed was limited (0.6 to 2.0%) and drug could only be detected in the CSF following a 10 mg/m(2 )dose. ZD1694 has a spectrum of activity that only partially overlaps with 5-fluorouracil (modulated with leucovorin) against colon tumours in vitro. ZD1694 has antitumour activity in mice. ZD1694 entered clinical study and has completed Phase I and II evaluation, with activity observed in several tumour types. Appreciable activity in the Phase II colorectal study (29% objective response rate on interim analysis) led to the current Phase III study, randomised against 5-fluorouracil/leucovorin.