Pharmacological Modulation of Fluoropyrimidines

摘要: Few drugs in the present pharmacopia of antineoplastic pharmacology have exemplified importance bench-to-bed paradigm that has become cornerstone present-day developmental chemotherapy. From its rational synthesis by Heidelberger 1957 (1) to quantification molecular determinants fluorinated pyrimidine (fluoropyrimidine) activity, our understanding fluoropyrimidine helped mold concepts everything from target-oriented drug development phenotyping, and resistance synergy. It is thorough biochemical 5-fluorouracil (5-FU) we learned how exploit this biochemistry improve cytotoxicity 5-FU. Regrettably, although augmented improved overall response rates time disease progression parameters select clinical trials, it infrequently results survival—the end-point probably matters most. Pharmacological modulation any revolves around those critical relationships between targets cell, can their underlying biology a way renders combination agents complementary. Over past 45 yr, tomes been written on virtually every aspect with regard fluoropyrimidines. I will not reiterate details experience. Rather, chapter, briefly review historical experience order provide context for formulation new approaches. Unquestionably, however, future innovations use fluoropyrimidines, or other class matter, be markedly essential elements drug’s pharmacology.