Generation of a set of simple, interpretable ADMET rules of thumb.

By Matthew Paul Gleeson. Journal of Medicinal Chemistry, 2008

869 citations recorded by the source corpus.

Subfields: Computational Theory and Mathematics, Oncology, Pharmacology

View Paper: https://www.semanticscholar.org/paper/ee8eec476fa2396d6f9d70e09d4a347ea6abd40a

How researchers see this paper

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

In Computational Theory and Mathematics

1. M. Hann
2. N. Abbott
3. Michael J. Waring
4. John A. Arnott
5. S. Planey

In Oncology

1. Behnam Noorani
2. N. Abbott
3. M. Hann
4. Michael J. Waring
5. L. Cucullo
6. Hossam Kadry
7. John A. Arnott
8. S. Planey

In Pharmacology

1. M. Hann
2. N. Abbott
3. Michael J. Waring
4. John A. Arnott
5. S. Planey

Citations in the corpus

• Molecular obesity, potency and other addictions in drug discovery (2011, background): “4) of an analysis that has led to the emergence of a further set of guidelines is the GSK 4/400 rule which relates to compounds with a CLogP less than 4 and a MW less than 400 and how on average they have a more favorable ADMET profile [6].”
• A blood–brain barrier overview on structure, function, impairment, and biomarkers of integrity (2020, background): “Studies showed that the negative effect of H bonds on drug permeability might be attributed to the significant increase in the free energy required for moving the drug from an aqueous phase into the lipid of the cell membrane [116, 122].”
• Structure and function of the blood-brain barrier. (2010, background): “Factors which restrict the entry of compounds into the CNS are a high polar surface area (PSA) (greater than 80 Å(2)), and a tendency to form more than 6 hydrogen bonds, a factor which greatly increases the free energy requirement of moving from an aqueous phase into the lipid of the cell membrane (”
• The role of ligand efficiency metrics in drug discovery (2014, neutral): “37(LLE/HA) (5) LELP = cLogP/LE (6) Equation 1 (REF.”
• Blood–brain barrier structure and function and the challenges for CNS drug delivery (2013, background): “brain:plasma ratio at steady-state (or logBB, also termed Kp) (Gleeson 2008), but this includes drug binding in plasma”
• Compilation and physicochemical classification analysis of a diverse hERG inhibition database (2016, neutral): “[13] analyzed more than 35,000 GSK compounds, and when these were split into three bins by log P values, the differences in average pIC50 values among the bins were much larger for bases and zwitterions compared to acids and neutral molecules.”
• The influence of lipophilicity in drug discovery and design (2012, background): “According to Lipinski, a limit of log P < 5 is a desirable lipophilicity range for compounds reaching Phase II clinical trials [4]; however, Gleeson has suggested that compounds with log P < 4 (and a molecular weight < 400) stand a much higher chance of success against a comprehensive set of ADMET p”
• Lipophilicity in drug discovery (2010, background): “Along these lines, it has been suggested that reduction of molecular weight [21,35,40], removal of aromatic rings [75] and increased saturation or added chirality [76] might offer generic means of achieving this.”