Lipinski´s Rule of 5
In 1997 Christopher Lipinski from Pfizer found a simple mnemonic which he called the "Rule of 5" because the parameter cut-off values all contained 5's. Numerically there actually are only four rules. This was a major breakthrough for the chemInformatic society. The Rule of 5 stated:
Poor absorption or permeation are more likely when there are:
1) More than 5 H-bond donors
2) The molecular weight is over 500
3) The CLog P is over 5 (or MLOGP is over 4.15)
4) The sum of N's and O's is over 10
Substrates for transporters and natural products are exceptions.
The rule is useful but it has some limitations. Some of today’s blockbusters fail by using that rule. It is too simple to detect all patterns of drugs. For further development’s, see expert systems for selecting molecules ==> Lead optimisation and drug-candidate selection
H-donors : 4
MLOGP: -0.09 (exp. LogP: -1.56)
H-acceptors : 8
Aciclovir would pass the Rule of 5.
Lipinski, C. A., Lombardo, F., Dominy, B. W., Feeney, P. J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings.
Adv. Drug Delivery Rev. 23, 1997, 3-25.
Lipinski, C. A. Drug-like properties and the causes of poor solubility and poor permeability.
J. Pharm. Tox. Meth. 44, 2000, 235-249.
PharmaInformatic and UNIZYME Laboratories sign cooperation agreement:
Selection and prioritisation of lead compounds for the treatment of autoimmune and inflammatory diseases based on estimated oral bioavailability in humans with IMPACT-F (more).
Read the answer here.