From: A perspective on multi-target drug discovery and design for complex diseases
Target | Parameters | Effects |
---|---|---|
Receptor (R) | \(L + R\mathop{\rightleftarrows}\limits_{k_{\text{off}}}^{k_{\text{on}}}LR \to {\text{conformational change}}\) | Multiple effects possible: on, off, partial, etc |
Enzyme (E) | Reversible \(L + E\mathop{\rightleftarrows}\limits_{k_{\text{off}}}^{k_{\text{on}}}{\text{LE}}\) Irreversible \(L + E \mathop{\rightleftarrows}\limits_{k_{\text{off}}}^{k_{\text{on}}}{\text{LE}}\xrightarrow{{k_{\text{inact}} }}L - E\) | Decreases product, prevents depletion of substrate but can be out-competed by substrate Inactivated enzyme; recovery depends on normal turnover of enzyme (minutes to days) |
Protein or DNA (M) | \(L + M\mathop{\rightleftarrows}\limits_{k_{\text{off}}}^{k_{\text{on}}}LM\) | Ligand and target often at same concentration in vitro. Outcome of binding best measured downstream |
Cell target (T) | \(L_{\text{out}}\xrightarrow{\text{cell uptake}}\,L_{\text{in}} \xrightarrow{\text{metabolism?}}\frac{\text{Organelle uptake}}{\text{Other binding}} \to L + T\mathop{\rightleftarrows}\limits_{k_{\text{off}}}^{k_{\text{on}}}{\text{LT}}\) | Concentration at target site unknown Major effects often easy to assess (e.g., cell death) but mechanism can be obscure |