Table 1.
General description of JAK inhibitors.
| JAK inhibitor | Anti-JAK2 IC50 [nM] | JAK selectivity (IC50 [nM]) | Non-JAK targets | Current phase | Tested diseases | Unique effects |
|---|---|---|---|---|---|---|
| INCB018424 (ruxolitinib) | 7.2 | JAK1 (1) JAK3 (98) TYK2 (9.3) |
– | III | PMF, PV, ET, cutaneous inflammation, leukemia, rheumatoid diseases | Response rates are similar regardless of MF subtype and regardless of JAK2V617F mutation presence |
| CEP701 (lestaurtinib) | 1 | JAK3 (3) | FLT3, TrkA | I/II | PMF, PV, ET, Hodgkin lymphoma, solid tumors, hematological malignancies, autoimmune diseases | Well tolerated; no decrease in JAK2V617F allele burden |
| SB1518 | 22 | JAK1 (58) JAK3 (24) |
FLT3 | I/II | PMF, lymphoma | Well tolerated; promising efficacy in symptomatic MF patients with splenomegaly |
| SAR302503 | 3 | JAK1 (35) JAK3 (332) TYK2 (135) |
FLT3, RET | I/II | PMF, mast cell leukemia | Improvement of baseline constitutional symptoms |
| XL019 | 2 | JAK1 (105) JAK3 (996) |
– | Discontinued | PMF, PV, post-PV/ET MF | Clinical studies discontinued due to high rate of neurotoxicity |
| CYT387 | 18 | JAK1 (0.6) JAK3 (8.6) |
JNK1, CDK2 | I/II | PMF, post-PV/ET MF | Significant improvement rates in anemia and splenomegaly, and it has a favorable toxicity profile |
| AZD1480 | 0.26 | JAK1 (5) JAK3 (15) |
TrkA, Aurora A, FGFR1 | I/II | PMF, post-PV/ET MF, glioblastoma, solid tumors | The first trial evaluating AZD1480 in humans is still ongoing |
| INCB028050 | 5.7 | JAK1 (5.9) | – | Preclinical | Rheumatoid arthritis (in rodent models) | – |
| INCB16562 | 0.3 | JAK1 (2.2) JAK3 (10.1) TYK2 (2.7) |
– | Preclinical | PMF, multiple myeloma | – |
| CP-690550 (Tasocitinib) | 250 | – | – | Preclinical | Rheumatic and autoimmune diseases, kidney transplantation, pulmonary eosinophilia, organ transplant rejection | – |
| NVP-BSK805 | – | – | – | Preclinical | PV | – |
ET, essential thrombocythemia; MF, myelofibrosis; PMF, primary myelofibrosis; PV, polycythemia vera.