Methylbenzoprim, a derivative of the antimalarial drug Pyrimethamine, is a non-classical potent inhibitor of mammalian dihydrofolate reductase (IC50 = 3.2 nM rat liver).1 It inhibited melanoma tumor growth both in vitro and in vivo.2 Methylbenzoprim has been recently found to also inhibit thymidylate synthase (TYMS) with activity comparable to the 5-FU metabolite FdUrd.3 It was more potent than 5-fluorouracil in a panel of 4 pancreatic ductal adenocarcinoma cells lines and without TYMS overexpression that frequently leads to drug resistance.3 Methylbenzoprim inhibited tumor growth and progression in two pancreatic cancer xenograft models. Orally bioavailable.
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