2 research outputs found
Discovery of a Novel 2,6-Disubstituted Glucosamine Series of Potent and Selective Hexokinase 2 Inhibitors
A novel series of potent and selective
hexokinase 2 (HK2) inhibitors,
2,6-disubstituted glucosamines, has been identified based on HTS hits,
exemplified by compound <b>1</b>. Inhibitor-bound crystal structures
revealed that the HK2 enzyme could adopt an “induced-fit”
conformation. The SAR study led to the identification of potent HK2
inhibitors, such as compound <b>34</b> with greater than 100-fold
selectivity over HK1. Compound <b>25</b> inhibits <i>in
situ</i> glycolysis in a UM-UC-3 bladder tumor cell line via <sup>13</sup>CNMR measurement of [3-<sup>13</sup>C]lactate produced from
[1,6-<sup>13</sup>C<sub>2</sub>]glucose added to the cell culture
Discovery of a Novel 2,6-Disubstituted Glucosamine Series of Potent and Selective Hexokinase 2 Inhibitors
A novel series of potent and selective
hexokinase 2 (HK2) inhibitors,
2,6-disubstituted glucosamines, has been identified based on HTS hits,
exemplified by compound <b>1</b>. Inhibitor-bound crystal structures
revealed that the HK2 enzyme could adopt an “induced-fit”
conformation. The SAR study led to the identification of potent HK2
inhibitors, such as compound <b>34</b> with greater than 100-fold
selectivity over HK1. Compound <b>25</b> inhibits <i>in
situ</i> glycolysis in a UM-UC-3 bladder tumor cell line via <sup>13</sup>CNMR measurement of [3-<sup>13</sup>C]lactate produced from
[1,6-<sup>13</sup>C<sub>2</sub>]glucose added to the cell culture