Table 1.
Properties of selected compounds with acceptable in vivo profiles.
| Compound properties | BLU4565 | BLU0556 | BLU7482 |
|---|---|---|---|
| MW | 461.5 | 413.5 | 420.5 |
| cLogP, cLogD | 4.6, 4.6 | 4.3, 4.3 | 3.6, 2.6 |
| TPSA | 97 | 92 | 97 |
| FaSSIF solubility (µM) | 100 | 32 | 100 |
| Mouse IV CL (mL/min/kg) (CLu) | 14.7 (381) | 26 (>3000) | 71.3 (552) |
| Mouse bioavailability (%F) | 100 | >50 | 77 |
| S(10) score | 0.077 | 0.107 | 0.045 |
CL, clearance; cLogP; partition coefficient; cLogD, distribution coefficient; FaSSIF, fasted state simulated intestinal fluid; IV, intravenous; MW, molecular weight; S(10) score, selectivity score defined by the fraction of kinases with PoC <10% when measured against KINOMEscan panel at 3 µM compound concentration; TPSA, total polar surface area.