ReviewBritish journal of pharmacology2016
On the different experimental manifestations of two-state 'induced-fit' binding of drugs to their cellular targets.
Review in British journal of pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
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Who cites it
10 citing papers in PubMed.
- Combining Fundamental Kinetics and Standard Alkylation Assays to Prioritize Lead-Like KRAS G12C Inhibitors.ACS omega · 2024Article
- Blocking the CGRP Receptor: Differences across Human Vascular Beds.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Ligand with Two Modes of Interaction with the Dopamine DACS chemical neuroscience · 2020Article
- Probe dependency in the determination of ligand binding kinetics at a prototypical G protein-coupled receptor.Scientific reports · 2019Article
- Link between a highMedChemComm · 2018Review
- A two-state model for the kinetics of competitive radioligand binding.British journal of pharmacology · 2018Article
- Drug-Target Kinetics in Drug Discovery.ACS chemical neuroscience · 2018Article
- Distinct in vivo target occupancy by bivalent- and induced-fit-like binding drugs.British journal of pharmacology · 2017Article
- Effects of target binding kinetics on in vivo drug efficacy: koff , kon and rebinding.British journal of pharmacology · 2016Article
- On the different experimental manifestations of two-state 'induced-fit' binding of drugs to their cellular targets.British journal of pharmacology · 2016Review
Corrections and comments
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
'Induced-fit' binding of drugs to a target may lead to high affinity, selectivity and a long residence time, and this mechanism has been proposed to apply to many drugs with high clinical efficacy. It is a multistep process that initially involves the binding of a drug to its target to form a loose RL complex and a subsequent isomerization/conformational change to yield a tighter binding R'L state. Equations with the same mathematical form may also describe the binding of bivalent antibodies and related synthetic drugs. Based on a selected range of 'microscopic' rate constants and variables such as the ligand concentration and incubation time, we have simulated the experimental manifestations that may go along with induced-fit binding. Overall, they validate different experimental procedures that have been used over the years to identify such binding mechanisms. However, they also reveal that each of these manifestations only becomes perceptible at particular combinations of rate constants. The simulations also show that the durable nature of R'L and the propensity of R'L to be formed repeatedly before the ligand dissociates will increase the residence time. This review may help pharmacologists and medicinal chemists obtain preliminary indications for identifying an induced-fit mechanism.
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