Figure 4. Key molecular-property trends for small molecules.

Comparisons of mean values of three key molecular properties, lipophilicity (LogP) (a), molecular weight (MW) (b) and polar surface areas (PSA) (c), are shown for CNS-penetrant small molecules (CNS; see Supplementary information S3 (table)), approved and marketed drugs for any indication (MKT; data from Vieth¹²¹) and kinase inhibitor drugs for all indications (KID; see Supplementary information S4 (table)). One-way ANOVA was used to evaluate significant differences to CNS mean values. Mean values for LogP (d), MW (e) and PSA (f) were also calculated for compounds in the CNS dataset (see Supplementary information S3 (table)) that are P-glycoprotein substrates (PGP⁺) compared with compounds that have been experimentally validated as non-P-glycoprotein substrates (PGP⁻). Student’s t-test was used to compare mean values. *p < 0.05. **p < 0.001.