Skip to content
Bending the Curve Trial by Trial
?

Pyrimidine analogues and fluoropyrimidinesUsed in a few countriesDerivative of an earlier drugNeeds review

Tegafur

Also known as ftorafur, FT-207, Futraful

An oral prodrug of fluorouracil, first made in Latvia in the 1960s and developed in Japan. It is the fluoropyrimidine component of two combinations, tegafur-uracil (UFT) and S-1.

From discovery to approval

  1. c. 1966 · Earliest report found

    A 2013 review says S. A. Hiller of the Riga institute in Latvia first synthesised tegafur in 1966; a 2009 review dates the synthesis by Hiller and colleagues to 1967, at the Latvian Institute of Organic Synthesis. The compound is 1-(2-tetrahydrofuryl)-5-fluorouracil. The original papers were not found.[2][1][3][4][5]

  2. No approval is recorded on this site.

How it works

A prodrug that releases fluorouracil gradually in the liver, by the microsomal enzyme CYP2A6 according to a 2009 review. The released fluorouracil then acts as described for that drug.[1]

Where it came from and why

A 2009 review calls it the first anticancer prodrug of fluorouracil. A 2013 review says its advantage is oral availability, with blood levels like those of continuous fluorouracil infusion. Neither source states the original motive.

Cancers

  • Solid tumours (preclinical and early development)

    A 1976 paper compared ftorafur with fluorouracil in mouse leukaemia and other tumour models. A 2009 review says the injectable form was developed up to phase II in the USA and then stopped. No single-agent indication was read.[3]

Family and partners

Derived from: Fluorouracil (5-FU)

Drugs derived from it: Tegafur-uracil (UFT), Tegafur-gimeracil-oteracil (S-1)

Worth knowing

  • A 2009 review by an S-1 developer says Taiho's president, Y. Kobayashi, saw an ampule of this fluorouracil derivative in Moscow in June 1969, received a sample, and introduced it into Japan in December that year.[1]
  • The same review says it was first introduced in 1970 as an injectable drug, which caused nausea, vomiting, rash and central nervous system disturbances, and that oral administration was then proposed by Kimura, Fujii and Taguchi.[1]
  • A 2013 review says it was introduced clinically in Japan in 1974 as the first oral anticancer drug in the world; the two reviews describe the sequence of injectable and oral introduction differently.[2]
  • In a 1976 mouse study, fluorouracil produced greater increases in lifespan than ftorafur in L1210 leukaemia, and ftorafur was ineffective in P388 leukaemia, which is sensitive to fluorouracil.[3]
  • A 2023 review credits Setsuro Fujii with developing tegafur, UFT, S-1 and trifluridine-tipiracil.[4]

References

  1. Shirasaka T. Development history and concept of an oral anticancer agent S-1 (TS-1): its clinical usefulness and future vistas. Jpn J Clin Oncol. 2009;39(1):2-15. PubMedDOI
  2. Utsugi T. New challenges and inspired answers for anticancer drug discovery and development. Jpn J Clin Oncol. 2013;43(10):945-53. PubMedDOI
  3. Garibjanian BT, Johnson RK, Kline I, Vadlamudi S, Gang M, Venditti JM, et al. Comparison of 5-fluorouracil and ftorafur. II. Therapeutic response and development of resistance in murine tumors. Cancer Treat Rep. 1976;60(9):1347-61. PubMed
  4. Maehara Y, Oki E, Ota M, Harimoto N, Ando K, Nakanishi R, et al. Lineage of drug discovery research on fluorinated pyrimidines: chronicle of the achievements accomplished by Professor Setsuro Fujii. Int J Clin Oncol. 2023;28(5):613-624. PubMedDOI
  5. Yamashita K, Sutou H, Maruden A, Takenouchi T, Morita K, Ariyoshi T. A nine-month chronic toxicity study of tegafur-uracil mixture (UFT) in dogs. J Toxicol Sci. 1988;13(2):97-132. PubMedDOI
  6. Wellington K, Goa KL. Oral tegafur/uracil. Drugs Aging. 2001;18(12):935-48; discussion 949-50. PubMedDOI