O ( )n
n 1 2 3 4
IC50 (ď M) 3.9 0.31 110 100
IC50 values are not equilibrium constants, but they are related to equilibrium constants throught the Cheng-Prussoff equation, which was first introduced back in Chapter 4. One can, however, compare IC50 values of two compounds to determine relative binding energies. The only precaution is that the IC50 values must be determined using the same conditions in the same assay â€“ same enzyme substrate at constant concentration.
The difference in binding energy (BE) between the linked compounds for n = 1 and n = 2 can be determined to be 1.5 kcal/mol.
Original reference: Hajduk, P. J.; Sheppard, G.; Nettesheim, D. G.; Olejniczak, E. T.; Shuker, S. B.; Meadows, R. P.; Stelnman, D. H.; Carrera, Jr., G. M.; Marcotte, P. A.; Severin, J.; Walter, K.; Smith, H.; Gubbins, E.; Simmer, R.; Holzman, T. F.; Morgan, D. W.; Davidsen, S. K.; Summers, J. B.; Fesik, S. W. Discovery of Potent Nonpeptide Inhibitors of Stromelysin Using SAR by NMR. J. Am. Chem. Soc. 1997, 119, 5818-5827.