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UFT

Merck KGaA

Drug Names(s): tegafur/uracil

Description: UFT (tegafur-uracil) consists of tegafur and uracil combined in a 1:4 molar ratio. Tegafur is a 5-FU prodrug, which means it is metabolized after administration into the active compound5-FU. Uracil is a natural substrate for the liver enzyme dihydropyrimidinedehydrogenase (DPD). By competing with 5-FU for DPD, uracil inhibits its degradation,resulting in sustained higher 5-FU levels in tumor cells.

5-Fluorouracil exerts its cytotoxicity mainly following its conversion, by a two-step route, to 5-fluoro-uridine monophosphate (5-FUMP). 5-FUMP is further transformed to 5-FdUMP, an irreversible inhibitor of thymidylate synthase. This binding inhibits the formation of thymidylate from 2’-deoxyuridylate. Thymidylate is the necessary precursor of thymidine triphosphate, which is essential for the synthesis of DNA, so that a deficiency of this compound can inhibit cell division. Second, nuclear transcriptional enzymes can mistakenly incorporate FUTP in place of uridine triphosphate (UTP) during the synthesis of RNA. This metabolic error can interfere with RNA processing and protein synthesis.

Deal Structure: In May 1995, Bristol-Myers Squibb and Taiho Pharmaceutical, a subsidiary of Otsuka Holdings, announced an agreement in which Bristol-Myers Squibb will obtain exclusive rights to UFT (tegafur and uracil) in most parts of the world.

In July 2005, Merck KGaA announced that it will acquire most of the global rights for UFT from Taiho Pharmaceutical of Japan. Merck acquired UFT after Bristol-Myers Squibb returned the worldwide rights of the product to Taiho Pharmaceutical. Taiho will supply the capsules to Merck for its territories and will retain rights in Japan, South Korea, Taiwan, Malaysia and Singapore.

In January 2007, the acquisition of Serono S.A. (now Merck Serono S.A.) by Merck KGaA and the integration of the business with the former Merck KGaA Ethicals Division was completed. Merck Serono is now the division of Merck KGaA which specializes in prescription pharmaceuticals. Its North American business operates in the United States and Canada under EMD Serono.

Partners: Otsuka Holdings Co., Ltd.


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