Table 1.
Structure–activity relationships predict CNS penetrance
| Test article | MW | cLogP | LogD (pH 7.4) | H-donors | PSA | pKa | CNS MPO |
|---|---|---|---|---|---|---|---|
| Tolebrutinib | 455.5 | 2.69 | 2.53 | 1 | 92.0 | 6.55 | 4.73 |
| Ibrutinib | 440.5 | 2.92 | 2.92 | 1 | 99.2 | 3.95 | 4.41 |
| Evobrutinib | 429.5 | 3.19 | 3.19 | 2 | 93.4 | 6.42 | 4.20 |
| Fenebrutinib | 664.8 | 1.59 | 1.57 | 2 | 119.3 | 7.55 | 3.52 |
| BIIB091 | 542.6 | 0.20 | 0.19 | 2 | 127.9 | 6.75 | 3.50 |
| Remibrutinib | 507.5 | 3.29 | 3.29 | 2 | 110.4 | 5.65 | 3.03 |
The multi parameter optimization (MPO) score is an in silico tool to estimate the ability of a molecule to penetrate the blood–brain barrier on the basis of its chemical properties, including molecular weight (MW), calculated partition coefficient (cLogP), ionizable distribution coefficient (LogD), the number of hydrogen bond donor (H-donors), the polar surface area (PSA), and the acid dissociation constant (pKa)