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Design of a novel oral fluoropyrimidine carbamate, capecitabine, which generates 5-fluorouracil selectively in tumours by enzymes concentrated in human liver and cancer tissue.
Capecitabine, which is finally converted to 5-FU by dThdPase in tumours, should be much safer and more effective than5-FU, and this was indeed the case in the HCT116 human colon cancer and the MX-1 breast cancer xenograft models. Expand
Host sphingolipid biosynthesis as a target for hepatitis C virus therapy
NA255 is a new anti-HCV replication inhibitor that targets host lipid rafts, suggesting that inhibition of sphingolipid metabolism may provide a new therapeutic strategy for treatment of HCV infection. Expand
The design and synthesis of a new tumor-selective fluoropyrimidine carbamate, capecitabine.
In tests with various human cancer xenograft models, capecitabine was more efficacious at wider dose ranges than either 5-FU or 5'-DFUR and was significantly less toxic to the intestinal tract than the others in monkeys. Expand
Design and synthesis of novel allosteric MEK inhibitor CH4987655 as an orally available anticancer agent.
The design and synthesis of a novel MEK inhibitor, based on the 3D-structural information of the target enzyme, and then multidimensional optimization including metabolic stability, physicochemical properties and safety profiles were effectively performed led to the identification of a clinical candidate for an orally available potent MEK inhibitors, CH4987655. Expand
Identification of a Novel Inhibitor Specific to the Fungal Chitin Synthase
It appears that in C. albicans, inhibition of CaChs1p causes cell growth arrest, but simultaneous inhibition ofCaCHS1p and CaChS2p is lethal, and a novel inhibitor is identified and characterized that was highly specific to Ca chitin synthases. Expand
Crystal structures of Candida albicans N-myristoyltransferase with two distinct inhibitors.
Myristoyl-CoA:protein N-myristoyltransferase (Nmt) is a monomeric enzyme that catalyzes the transfer of the fatty acid myristate from myristoyl-CoA to the N-terminal glycine residue of a variety ofExpand
Synthesis and biological activities of benzofuran antifungal agents targeting fungal N-myristoyltransferase.
The C-4 side chain modification of lead compound 1 has resulted in the identification of a potent and selective Candida albicans N-myristoyltransferase (CaNmt) inhibitor RO-09-4609, which exhibits antifungal activity in vivo and computer aided drug design, synthesis, structure-activity relationships, and biological properties of RO-9-4879. Expand
In vitro activity of isavuconazole against 140 reference fungal strains and 165 clinically isolated yeasts from Japan.
Isavuconazole showed very good in vitro antifungal activity with a broad spectrum, including against FLC-resistant Candida spp. Expand
Synthesis and structure-activity relationships of novel fungal chitin synthase inhibitors.
A novel Candida albicans chitin synthase 1 (CaChs1) inhibitor, RO-41-0986 (1) was discovered by random screening. Systematic modification led to the identification of a highly potent CaChs1Expand
Design and synthesis of novel benzofurans as a new class of antifungal agents targeting fungal N-myristoyltransferase. Part 1.
Modification of the C-4 side chain of 1 has led to the discovery of a potent and selective CaNmt inhibitor 11 (RO-09-4609), which exhibits antifungal activity against C. albicans in vitro. Expand