Preliminary clinical observations in selected JAK2 inhibitor trials.
| Agent . | Company . | Target(s) . | JAK IC50(nM) . | Current phase . | Preliminary clinical observations in myelofibrosis studies . |
|---|---|---|---|---|---|
| *Assays performed at 1 mM ATP concentration. | |||||
| INCB018424 | Incyte | JAK1, JAK2 | JAK1 = 2.7* JAK2 = 4.5* JAK3 = 322* | III | Decreased spleen size irrespective of JAK2 mutational status; improved quality of life, weight and performance; decreased inflammatory cytokine levels. Myelosuppression. |
| TG101348 | TargeGen | JAK2 | JAK1 = 105 JAK2 = 3 JAK3 = 996 | II | Decreased spleen size; decrease in WBC. Myelosuppression; gastrointestinal disturbance. |
| XL019 | Exelixis | JAK2 | JAK1 = 132 JAK2 = 2 JAK3 = 250 | discontinued | Decreased spleen size only in patients with JAK2 V617F or MPL mutation; decreased pruritis and improved fatigue. Neurotoxicity. |
| CEP701 (lestaurtinib) | Cephalon | JAK2, FLT3 | JAK2 = 1 | I/II | Decreased spleen size, improvement in blood cell count. Myelosuppression; gastrointestinal disturbance. |
| Agent . | Company . | Target(s) . | JAK IC50(nM) . | Current phase . | Preliminary clinical observations in myelofibrosis studies . |
|---|---|---|---|---|---|
| *Assays performed at 1 mM ATP concentration. | |||||
| INCB018424 | Incyte | JAK1, JAK2 | JAK1 = 2.7* JAK2 = 4.5* JAK3 = 322* | III | Decreased spleen size irrespective of JAK2 mutational status; improved quality of life, weight and performance; decreased inflammatory cytokine levels. Myelosuppression. |
| TG101348 | TargeGen | JAK2 | JAK1 = 105 JAK2 = 3 JAK3 = 996 | II | Decreased spleen size; decrease in WBC. Myelosuppression; gastrointestinal disturbance. |
| XL019 | Exelixis | JAK2 | JAK1 = 132 JAK2 = 2 JAK3 = 250 | discontinued | Decreased spleen size only in patients with JAK2 V617F or MPL mutation; decreased pruritis and improved fatigue. Neurotoxicity. |
| CEP701 (lestaurtinib) | Cephalon | JAK2, FLT3 | JAK2 = 1 | I/II | Decreased spleen size, improvement in blood cell count. Myelosuppression; gastrointestinal disturbance. |