ADMETlab 3.0 Output

For the output, we are going to talk about the most important one.

Physicochemical Properties

Aspirin as a case study

Molecular Weight (MW)

• Definition: Is the sum of the atomic masses of all atoms in a molecule. For aspirin (C₉H₈O₄), MW = 180.04 g/mol.

• Importance: Molecular weight influences membrane permeability and oral bioavailability of the drug candidate. Lower molecular weight compounds generally have better absorption characteristics, and it is always desirable.

• Expected Range: Optimal range is 100-600 g/mol based on Drug-Like Soft rules on the ADMETlab database. Aspirin's MW of 180.04 falls within this ideal range (Figure 1).

Number of Hydrogen Bond Acceptors (nHA)

• Definition: Count of oxygen and nitrogen atoms that can accept hydrogen bonds. Aspirin has four oxygen atoms (nHA = 4).

• Importance: Affects permeability and solubility. Excessive H-bond acceptors can reduce membrane permeability.

• Expected Range: Optimal range is 0-12. Aspirin's value of 4 is well within acceptable limits (Figure 1). 

Number of Hydrogen Bond Donors (nHD)

• Definition: Count of OH and NH groups that can donate hydrogen bonds. Aspirin has 1 carboxylic acid group (nHD = 1).

• Importance: Influences membrane penetration and solubility. Higher numbers can decrease permeability.

• Expected Range: Optimal range is 0-7. Aspirin's value of 1 is favorable (Figure 1).

Number of Rotatable Bonds (nRot)

• Definition: Count of bonds that allow free rotation. Aspirin has 3 rotatable bonds.

• Importance: Affects molecular flexibility and oral bioavailability. Fewer rotatable bonds often correlate with better permeability.

• Expected Range: Optimal range is 0-11. Aspirin's value of 3 is acceptable (Figure 1).

Topological Polar Surface Area (TPSA)

• Definition: Sum of surface contributions from polar atoms (O, N, and attached H atoms). Aspirin's TPSA is 63.6 Ų.

• Importance: Key predictor of cell permeability and oral bioavailability. Lower TPSA values generally favor better absorption.

• Expected Range: Optimal range is 0-140 Ų. Aspirin's value of 63.6 Ų indicates good permeability potential.

Logarithm of Partition Coefficient (logP)

• Definition: Measure of lipophilicity, representing the ratio of a compound's solubility in n-octanol versus water. Aspirin's logP is approximately 1.2.

• Importance: Influences membrane permeability, distribution, and binding to receptors. Either too high or too low values can be problematic.

• Expected Range: Optimal range is 0-3 log units. Aspirin's logP of 1.16 indicates a good balance between hydrophilicity and lipophilicity. 

Logarithm of Distribution Coefficient at pH 7.4 (logD₇.₄)

• Definition: logP adjusted for ionization at physiological pH (7.4). Aspirin's logD₇.₄ is approximately 1.22 due to partial ionization of its carboxylic acid group.

• Importance: Better predictor of lipophilicity at physiological conditions than logP, affecting membrane partitioning and distribution.

• Expected Range: Optimal range is 1-3 log units. Aspirin's value of 1.22 is slightly below ideal but still acceptable (Figure 1).

Aqueous Solubility (logS)

• Definition: Logarithm of molar solubility in water. Aspirin's logS is approximately -1.55.

• Importance: Critical for drug absorption as compounds must dissolve before being absorbed. Low solubility can limit oral bioavailability.

• Expected Range: Optimal range is -4 to 0.5 log mol/L. Aspirin's value of -1.55 indicates moderate solubility.

Number of Rings (nRing): Count the number of ring systems. Aspirin has one ring (benzene), and the ideal range is between 0-6; the number of rings influences structural complexity and binding.

Number of Heteroatoms (nHet): Count the number of non-carbon atoms. Aspirin has four oxygen atoms, and the ideal range is between 1-15; the number of nHet can affect polarity and drug-likeness.

Formal Charge (fChar): Count the net charge on the molecule. Aspirin has 0 (neutral), and the ideal range is -4 to 4. Formal charge impacts solubility and membrane permeability.