offrate

Off-rate, in the context of chemical kinetics and biophysics, refers to the rate constant for the dissociation of a bound complex, typically a ligand from a receptor or an antigen from an antibody. Denoted k_off, it has units of s^-1 and governs the decline of the bound state [P-L] over time according to d[P-L]/dt = -k_off [P-L]. The average lifetime of the bound complex is τ = 1/k_off. The binding affinity, described by the equilibrium dissociation constant K_d, relates to k_off and the association rate constant k_on by K_d = k_off / k_on. A small k_off corresponds to a long residence time on the target, which can influence pharmacodynamics and signaling duration.

Measurement and interpretation of off-rate are central in binding kinetics. Common methods to measure k_off include surface plasmon resonance (SPR) and bio-layer interferometry (BLI), which monitor dissociation after switching to buffer; stopped-flow or rapid-mixing techniques can extract kinetic rates from multiple phases; ITC can provide thermodynamic parameters but is less direct for k_off unless coupled with kinetic analysis. Off-rate is sensitive to conditions such as temperature, pH, salt, and conformational states; measured values are often reported for specific experimental setups.

In drug design, residence time (1/k_off) is a consideration; too fast k_off may require higher doses to maintain efficacy, while too slow k_off could lead to prolonged target engagement and slower clearance. There is ongoing research about optimizing both k_on and k_off to improve selectivity and therapeutic outcomes.