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• W1989405594 abstract "Small molecules that inhibit the geranylgeranylation of K-Ras4B and RhoA by protein geranylgeranyltransferase type I (GGTase-I) were identified from chemical genetic screens of heterocycles synthesized through phosphine catalysis of allenes. To further improve the efficacy of the GGTase-I inhibitors (GGTIs), 4288 related compounds bearing core dihydropyrrole/pyrrolidine and tetrahydropyridine/piperidine scaffolds were synthesized on SynPhase lanterns in a split-pool manner through phosphine-catalyzed [3 + 2] and [4 + 2] annulations of resin-bound allenoates. Testing of the 4288 analogues resulted in several GGTIs exhibiting submicromolar IC50 values. Because proteins such as Ras and Rho GTPases are implicated in oncogenesis and metastasis, these GGTIs might ultimately lead to the development of novel antitumor therapeutics." @default.
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• W1989405594 date "2007-04-17" @default.
• W1989405594 modified "2023-10-01" @default.
• W1989405594 title "Small-Molecule Inhibitors of Protein Geranylgeranyltransferase Type I" @default.
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• W1989405594 doi "https://doi.org/10.1021/ja070274n" @default.
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