What is your criteria for drug-like library against non-CNS target?

I came across a very interesting project which led me to ask this question. I have been happily following 'Lipinski rule of 5' i.e. MW<500, HBD<5, HBA<10 and logP<5, for years.

While upper limits from Lipinski rule of 5 (e.g. mol. weight <500 or HBD<5) are justified. What should be the lower limit?

I have compiled the overall criteria for drug-like library against non-CNS target, which I surveyed from different literature and thought to use for my work;

Hydrogen bond donor: <5
Hydrogen bond acceptor: <10
Molecular weight: >=140 - <= 500 Da
logP: >=2 - <= 5
Rotatable bonds:<10 (Veber rule)
Topological polar surface area (TPSA): >=120 - <= 140 ?2

I am  eagerly waiting to hear  your comments, corrections and suggestions (specially from Pharmacokinetics and DMPK professionals).

Dr. Mahesh Kumar Teli

Assistant Professor Research, Gachon University

9 年

We should not be very particular for all the rules except MW in initial screening. Other rules should be adjusted according to the target requirement and we should not generalize them.

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