The 'rule of three' for fragment-based drug discovery: where are we now?

271 citations recorded by the source corpus.

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

A Role for Fragment-Based Drug Design in Developing Novel Lead Compounds for Central Nervous System Targets (2015, background): “Recently, the usefulness of this rule of three has been a subject of debate (30, 31).”
Twenty years on: the impact of fragments on drug discovery (2016, background): “Hence, a simple fragment with a limited number of potential interactions is relatively unconstrained when exploring the protein surface as it only needs to make one or two highly efficient interactions in order to bind 22 .”
In silico methods and tools for drug discovery (2021, background): “In general, the “ rule of three ” is commonly used to construct druggable fragments [180]: a molecular weight 300 Da, a cLogP ≤ 3, hydrogen bond donors ≤ 3, and hydrogen bond acceptors ≤ 3 [178 – 180].”
Key Topics in Molecular Docking for Drug Design (2019, methodology): “Secondly, Harren Jhoti’s group has suggested an adjusted set of rules [148] (or guidelines [149]), termed Rule of Three (RO3), derived from hits obtained via High Throughput X-ray Crystallography (HTX) and inspired by Lipinski’s Rule of Five [150].”