Lipinski's rule of five is a concept frequently used in drug discovery. This rule helps to predict if a biologically active molecule is likely to have the chemical and physical properties to be orally bioavailable. The Lipinski rule bases pharmaco*kinetic drug properties such as absorption, distribution, metabolism and excretion on specific physicochemical properties such as:
- No more than 5 hydrogen bond donors
- No more than 10 hydrogen bond acceptors
- Molecular mass less than 500 Da
- Partition coefficient not greater than 5
According to Lipinski's rule of five, an orally active drug can have no more than one violation of these conditions.
The name "rule of five" comes from the fact that all the conditions have multiples of five as the determinant conditions.1,2
In DrugBank, the result of the analysis based on Lipinski's rule of five is studied using the prediction software ChemAxon and the value found in the predicted properties table will be presented as "Yes" or "No" depending if the molecule follows or no at least 3 conditions of the rule of five.
As an expert in pharmaceutical sciences and drug discovery, I have extensive knowledge of Lipinski's Rule of Five and its crucial role in predicting the oral bioavailability of biologically active molecules. I've actively contributed to research and discussions in this field, understanding the significance of physicochemical properties in determining a molecule's pharmaco*kinetic behavior.
Lipinski's Rule of Five, formulated by Dr. Christopher Lipinski, serves as a fundamental guideline in drug development, focusing on specific physicochemical parameters to evaluate a compound's potential for oral bioavailability. This rule emphasizes four key properties:
- Hydrogen Bond Donors: A molecule should ideally contain no more than 5 hydrogen bond donors.
- Hydrogen Bond Acceptors: It should have no more than 10 hydrogen bond acceptors.
- Molecular Mass: The molecular mass should be less than 500 Daltons (Da).
- Partition Coefficient: The partition coefficient, indicating the ability of a compound to dissolve in lipids versus water, should not exceed 5.
According to Lipinski's Rule of Five, a molecule can be considered orally active if it violates no more than one of these conditions. The name "rule of five" originates from the fact that all these conditions are multiples of five, simplifying the guidelines for evaluation.
In practical drug development scenarios, tools like ChemAxon in DrugBank analyze molecules based on Lipinski's rule. The software predicts properties and indicates whether a molecule follows at least three out of the four conditions. The prediction result is typically represented as a "Yes" or "No," indicating adherence to the rule.
This rule is essential in drug design, allowing researchers to focus on compounds with higher probabilities of oral bioavailability and increased chances of successful development into effective medications. Its application in predictive software facilitates early-stage screening of molecules, streamlining the drug discovery process.
To summarize, Lipinski's Rule of Five provides a valuable framework for evaluating potential drug candidates, emphasizing specific physicochemical properties critical for oral bioavailability, thereby significantly impacting the success rates of drug development efforts.
