Table 2.
Relative kinase profiles comparing pacritinib, momelotinib, ruxolitinib, and fedratinib
| Kinase | IC50 (nM)
|
IC50 at 1 µM34
|
||
|---|---|---|---|---|
| Pacritinib | Momelotinib32,33 | Ruxolitinib | Fedratinib | |
| JAK-associated kinases | ||||
| JAK1 | + | ++++ | ++ | ++ |
| JAK2 | ++++ | ++++ | ++ | ++ |
| JAK2 (V617F) | ++++ | + | NR | NR |
| FLT3 | ++++ | +++ | NR | NR |
| FLT3 (ITD) | ++++ | NR | NR | ++ |
| FLT3 (D835Y) | ++++ | NR | NR | ++ |
| TYK2 | +++ | NR | ++ | ++ |
| JAK3 | ++++ | + | ++ | ++ |
| Non-JAK tyrosine kinases | ||||
| TRKC | ++++ | NR | NR | NR |
| TNK1 | ++++ | NR | NR | NR |
| ROS1 | ++++ | ++ | NR | NR |
| c-kit | +++ | NR | NR | NR |
| c-src | +++ | + | NR | NR |
| CSF1R (c-fms) | +++ | ++ | NR | NR |
| Nontyrosine kinases of interest | ||||
| HIPK4 | ++++ | ++ | NR | NR |
| IRAK1 | ++++ | NR | NR | NR |
Notes: Pacritinib scale: ++++, <25 nM; +++, 25 to <50 nM; +, >100 nM. Momelotinib scale: ++++, <25 nM32; +++, <100 nM; ++, <1 µM; +, >1 µM.33 Ruxolitinib and fedratinib scales: ++, IC50 at 1 µM.
Abbreviations: CSF1R, colony-stimulating factor 1 receptor; FLT3, fms-like receptor tyrosine kinase 3; HIPK4, homeodomain-interacting protein kinase 4; IC50, half maximal inhibitory concentration; IRAK1, interleukin-1 receptor-associated kinase 1; ITD, internal tandem duplication; JAK, Janus kinase; NR, not reported; TNK1, tyrosine kinase nonreceptor 1; TYK2, tyrosine kinase 2.