Polar surface area

Molecules with a polar surface area of greater than 140 angstroms squared (Å2) tend to be poor at permeating cell membranes.

[1] For molecules to penetrate the blood–brain barrier (and thus act on receptors in the central nervous system), a PSA less than 90 Å2 is usually needed.

By analyzing a drug candidate's TPSA, scientists can predict its potential for oral bioavailability and ability to reach target sites within the body.

Drugs with a lower TPSA (generally below 90 Ų) tend to permeate the BBB more easily, allowing them to reach the brain and exert their therapeutic effects (Shityakov et al[3]., 2013).

Similarly, for drugs intended to treat the fetus, a lower TPSA (below 60 Ų) is preferred to ensure they can pass through the placenta (Augustiño-Roubina[4] et al., 2019).