Figure 3

Applications of selectivity entropy. (a) Inhibitors that modify kinase conformation have higher selectivity. (b) Non-steroidal nuclear receptor antagonists are not more selective than steroidal antagonists. OHflu: hydroxyflutamide, ralx: raloxifene, 4OHT: 4-hydroxytamoxifen, PPT: propyl pyrazole triol, DES: diethylstilbestrol. Horizontal lines and dotted lines in panels (a) and (b) represent the average and median of each set, respectively. P values of two-tailed student-t tests are indicated. (c) Rank-ordering of hit selectivity in a panel of regulators of G-protein signalling. (d) Selectivity entropy of kinase inhibitors in clinical phase. Black bars: average entropy in that class. Light grey to white bars: averages restricted to oncology. Dark to light grey bars: averages for compounds of which the phase I trials were initiated before 2005. Error bars indicate one standard deviation. Numbers of datapoints used (column left to right): 10/8/6, 6/6/4, 6/4/4, 8/8/7. The discontinued class represent compounds that underwent clinical testing but were stopped. For the post-2005 projects, discontinued compounds have a lower entropy than the combined set of Phase III and launched compounds. As the number of non-oncology compounds is 2, 0, 2, 0 for each clinical bin respectively, this dataset only allows conclusions for the field of oncology.