In vitro activity and PK profiles of compounds 3, 4, and 5 (ref. 41).
| Compound code | IC50 selectivity index | Solubilitya (μg mL−1) | IC50 (μM) | GI50 (μM) | PAMPA Pappb (× 10−6 cm s−1) | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| JAK1/JAK2 | JAK3/JAK2 | TYK2/JAK2 | CDK2/JAK2 | CYP3A4 | CYP2D6 | Ba/F3-JAK2 V617F | MV4-11 | |||
| 3 | 143 | 13 | 8.1 | >1000 | >150 | 2.5 | >10 | 0.18 | 0.051 | 16.8 |
| 4 | >500 | 47 | 9.5 | >500 | 60.83 | >10 | >10 | 0.10 | 0.085 | 10.1 |
| Pacritinib 5 | 56 | 23 | 2.2 | 170 | >150 | >5 | >5 | 0.16 | 0.047 | 9.3 |
a
High throughput solubility in PBS buffered at pH 7.0.
b
PAMPA: parallel artificial membrane permeability assay.