Carboranes increase the potency of small molecule inhibitors of nicotinamide phosphoribosyltranferase.
Herein we report the use of carboranes to significantly increase the potency of small molecule inhibitors of nicotinamide phosphoribosyltranferase (Nampt), an enzyme that is central to metabolism and cell survival. We compare the inclusion of carborane with other similarly sized substituents and demonstrate that, compared with their purely organic counterparts, these molecules exhibit up to 10-fold greater antiproliferative activity against cancer cells in vitro and a 100-fold increase in Nampt inhibition.
Department of Chemistry, University of Missouri, Columbia, Missouri 65211, United States. leemw@missouri.edu
Mark W
MW
Lee
Yulia V
YV
Sevryugina
Aslam
A
Khan
Shui Q
SQ
Ye
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001880:Boranes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D054409:Nicotinamide Phosphoribosyltransferase / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D001880:Boranes; D054409:Nicotinamide Phosphoribosyltransferase