The
SCORE calculated and posted in this database is defined as the number of
parameters (out of four) that are less than or equal to the cut-off values
originally proposed by Lipinski’s “Rule of Five.”
This database developed this
score to aid the user with searching for compounds that potentially may have
good absorption or permeability properties (oral bioavailability). These scores
are only a prediction about a compound’s oral bioavailability and other criteria
should be considered when determining a compound’s usefulness as a drug.
Exceptions will always exist such as substrates for transporters and natural
products.
|
SCORE = Number of
Parameters (out of 4) Satisfying Lipinski’s “Rule of
Five” |
Lipinski’s “Rule of
Five” Prediction for a Compound’s ABSORPTION OR PERMEABILITY
PROPERTIES |
|
|
|
|
4 |
GOOD |
|
3 |
INDETERMINATE
|
|
2 |
INDETERMINATE
|
|
1 |
INDETERMINATE
|
|
0 |
POOR
|
Christopher Lipinski and his
co-authors reported a method of predicting a compound’s absorption or
permeability properties based on cut-off values for four parameters: LogP (where
P is the octanol-water partition coefficient), H-bond donors, H-bond acceptors
and the molecular weight. The “Rule of Five” is derived from the
observation that if all four parameter values for a compound are less than five
(LogP and H-bond donors) or multiples of five (ten for H-bond acceptors and five
hundred for molecular weight) then this compound is predicted to have good
absorption or permeability properties.
PARAMETER |
CUT-OFF
VALUES
(For
Good Absorption or Permeability Prediction) |
|
|
|
|
Log
P |
£
5 |
|
H-Bond
Donors |
£
5 |
|
H-Bond
Acceptors |
£
10 |
|
Molecular
Weight |
£
500 |
Please note: This database uses MDL’s QSAR Program to calculate LogP, H-bond donors and H-bond acceptors.
Reference:
Christopher A. Lipinski,
Franco Lombardo, Beryl W. Dominy and Paul J. Feeney,
”Experimental and
computational approaches to estimate solubility and permeability in drug
discovery and development settings.” Adv. Drug Delivery Rev., 1997, 23(1-3),
3-25.
Link for further information
on Lipinski’s “Rule of Five”