Biochemical Medicine and Metabolic Biology
Calculation of inhibitor Ki and inhibitor type from the concentration of inhibitor for 50% inhibition for Michaelis-Menten enzymes
References (6)
- et al.
Biochem. Med.
(1983) - et al.
Clin. Chim. Acta
(1968)
Cited by (66)
Enzymatic kinetics of photosystem II with DCBQ as a substrate in extended Michaelis-Menten model
2023, Journal of Photochemistry and Photobiology B: BiologyEnzyme kinetics by real-time quantitative NMR (qNMR) spectroscopy with progress curve analysis
2022, Analytical BiochemistryKinetic mechanisms of covalent inhibition
2021, Annual Reports in Medicinal ChemistryCitation Excerpt :The same principle applies to covalent inhibition as although the protein is irreversibly inhibited once the covalent E-I complex has formed, the initial reversible binding event to form the EI complex will still be affected by the substrate concentration and the inhibitor's mechanism of action. If the mechanism of action for the reversible step of covalent inhibition is known, the apparent KI may be corrected for substrate concentration.32,62,63 Due to limitations with solubility of the substrate or sensitivity of the detection system (which may require the use of comparatively low or high concentrations of the substrate relative to its KM) it is not always possible to run an assay at a substrate concentration equivalent to KM.32,33
Kinetic modelling of in vitro data of PI3K, mTOR1, PTEN enzymes and on-target inhibitors Rapamycin, BEZ235, and LY294002
2017, European Journal of Pharmaceutical SciencesCitation Excerpt :These relations can be also used in the analysis of variation in the IC50 values for LY294002 and BEZ235 inhibitors in cancer lines characterizing by different ATP levels (Moreno-Sánchez et al., 2014; Zhou et al., 2012). Note that according to the model of mTOR1 kinase (Eqs. (1) and (2)) and general properties of MM approximation (Brandt et al., 1987; Yung-Chi and Prusoff, 1973) the IC50 value for allosteric inhibitor Rapamycin does not depend on ATP concentration and its IC50 is equal to the dissociation constant of Rapamycin Kd,Rap in relation to Eq. (6). This result is in agreement with experimental IC50 values (2 nM and 7 nM for S6K1 and 4EBP1 respectively) which are close to theoretical dissociation constants Kd,Rap = 1.5 ± 0.5 nM and 7 ± 1.1 nM respectively (Table 1).