Cheng-Prusoff relationship

This is a linear relation often referred to as the Cheng-Prusoff relationship [5], It is characteristic of competitive ligand-receptor interactions. An example is shown in Figure 4.6b. 

As we stated above, there is a risk involved in the use of the Cheng-Prusoff relationships for SAR studies, as it is possible that structural alterations of the lead analogues could change the inhibition modality. This can be check from time to time for compounds that represent the greatest structural excursions from the lead molecule. Additionally compounds that are destined for progression into cellular and animal models should have their inhibition modality and affinity confirmed by running the more comprehensive studies discussed in Section 5.3. 

Y. Cheng and W. H. Prusoff, Relationship between the inhibition constant and the... 

Y.-C. Cheng and W. H. Prusoff, Relationship between the inhibition constant (K,) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an Enzymatic reaction, Biochem. Pharmacol 1973, 22, 3099-3108. 

The lower the IC50 or K, the higher the affinity. Results can also be expressed as a K, the inhibitory (or affinity) constant of the displacer compound for the receptor. and IC50 are not independent and are very simply related when the displacement is non-competitive (/T = IC50), but the relationship becomes more complicated (Cheng-Prusoff" equation) for a competitive displacement [/T = ICsq/) + [L]/A d) where [L] is the concentration of the radioactive ligand]. 

Cheng YC, Prusoff WH. Relationship between the inhibition 51. constant KI) and the concentration of inhibitor which causes... 

Cheng, Y. and Prusoff, W.H., Relationship between the Inhibitory Constant (Ki) and the Concentration of Inhibitor which Causes 50 Per cent Inhibition (IC50) of an Enzymatic Reaction, Biochem. Pharmacol., 22, 3099, 1973. 

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