How it began
The Institute of Organic Synthesis was founded in Riga in 1957 from three laboratories of the Latvian Academy of Sciences that were searching for new pharmaceuticals. Its initiator and director for 18 years was Solomon Hiller, a heterocyclic chemist known for bringing research results into practice. Ftorafur, later given the name tegafur, was introduced by S. Hiller, R. Zhuk and M. Lidak in 1964. It was patented in 1967 and approved for medical use in 1972.
How it works
Tegafur is a prodrug of the cancer drug 5-fluorouracil, known as 5-FU. It has no direct effect until the body metabolizes it into 5-FU, a step carried out by the enzyme CYP2A6. The 5-FU then blocks thymidylate synthase, an enzyme that cells need to make DNA. Researchers at the Riga institute described tegafur as having better bioavailability and lower toxicity than 5-FU itself.
How it spread
The Riga institute ran the whole cycle of drug development, from laboratory synthesis to industrial manufacture in its own experimental plant, and its medicines went to clinics in Latvia, Russia and other countries. The institute also began exporting products to Japan and France. Tegafur came into use in Japan, where a phase 3 trial reported in 2004 found that tegafur combined with uracil after surgery improved survival in lung cancer patients.
Where it stands today
Tegafur is a component of the combination drug tegafur and uracil, known as UFT, and of a combination with gimeracil and oteracil. It is used against cancers of the stomach, breast, lung, colon and rectum, head and neck, liver and pancreas. The UFT combination is not approved by the United States Food and Drug Administration but is widely used in other countries. The Riga institute, now the Latvian Institute of Organic Synthesis, reports 17 pharmaceuticals developed.
