JAK2 inhibitors that have made it to clinical trials in myelofibrosis and not terminated as yet
| Anti-JAK2 ATP mimetic . | Anti-JAK2 IC50 (JAK1/JAK3/TYK2 selectivity) . | Non-JAK kinase targets . | Clinical trials . | Disease features shown to be favorably affected . | Side effects . |
|---|---|---|---|---|---|
| INCB01842421 (phase 1/2 study) | 5.7nM (×1.0/×98/×9.3) | None of ∼ 28 kinases evaluated | MF (n = 153) 21 | Splenomegaly, constitutional symptoms, pruritus, cachexia | Thrombocytopenia (DLT) anemia, acute relapse of symptoms and re-enlargement of spleen on drug discontinuation, SIRS on drug discontinuation” |
| TG10134820 (phase 1/2 study) | 3nM (×35/×332/×135) | FLT3 RET | MF (n = 59) | Splenomegaly, constitutional symptoms, pruritus, leukocytosis, thrombocytosis, JAK2V617F burden | Increased amylase/lipase (DLT), anemia, thrombocytopenia, nausea/vomiting, diarrhea, increased transaminases |
| CEP-70177 (lestaurtinib) (phase 2 study) | 1nM (×?/×3/×?) | FLT3 TrkA | MF (n = 22) | Splenomegaly, anemia, pruritus | Diarrhea, nausea/vomiting, anemia, thrombocytopenia |
| CYT38778 (phase 1/2 study) | 18nM (×0.6/×8.6/×?) | JNK1 CDK2 | MF (n = 36) | Anemia, splenomegaly, constitutional symptoms, pruritus | Increased amylase/lipase (DLT), headache (DLT), thrombocytopenia, increased, transaminases, “first dose-effect characterized by transient hypotension and lightheadedness” |
| AZD148099 (phase 1/2 study) | 0.26nM (×5/×15/×?) | TrkA Aurora A FGFR1 | MF | Results pending | Results pending |
| SB1518100 (phase 1/2 study) | 22nM (×58/×24/×?) | FLT3 | MF (n = 31) | Splenomegaly | (DLT = GI symptoms), diarrhea, nausea thrombocytopenia |
| LY2784544 (phase 1/2 study) | Scant literature | Scant literature | MF | Results pending | Results pending |
| Anti-JAK2 ATP mimetic . | Anti-JAK2 IC50 (JAK1/JAK3/TYK2 selectivity) . | Non-JAK kinase targets . | Clinical trials . | Disease features shown to be favorably affected . | Side effects . |
|---|---|---|---|---|---|
| INCB01842421 (phase 1/2 study) | 5.7nM (×1.0/×98/×9.3) | None of ∼ 28 kinases evaluated | MF (n = 153) 21 | Splenomegaly, constitutional symptoms, pruritus, cachexia | Thrombocytopenia (DLT) anemia, acute relapse of symptoms and re-enlargement of spleen on drug discontinuation, SIRS on drug discontinuation” |
| TG10134820 (phase 1/2 study) | 3nM (×35/×332/×135) | FLT3 RET | MF (n = 59) | Splenomegaly, constitutional symptoms, pruritus, leukocytosis, thrombocytosis, JAK2V617F burden | Increased amylase/lipase (DLT), anemia, thrombocytopenia, nausea/vomiting, diarrhea, increased transaminases |
| CEP-70177 (lestaurtinib) (phase 2 study) | 1nM (×?/×3/×?) | FLT3 TrkA | MF (n = 22) | Splenomegaly, anemia, pruritus | Diarrhea, nausea/vomiting, anemia, thrombocytopenia |
| CYT38778 (phase 1/2 study) | 18nM (×0.6/×8.6/×?) | JNK1 CDK2 | MF (n = 36) | Anemia, splenomegaly, constitutional symptoms, pruritus | Increased amylase/lipase (DLT), headache (DLT), thrombocytopenia, increased, transaminases, “first dose-effect characterized by transient hypotension and lightheadedness” |
| AZD148099 (phase 1/2 study) | 0.26nM (×5/×15/×?) | TrkA Aurora A FGFR1 | MF | Results pending | Results pending |
| SB1518100 (phase 1/2 study) | 22nM (×58/×24/×?) | FLT3 | MF (n = 31) | Splenomegaly | (DLT = GI symptoms), diarrhea, nausea thrombocytopenia |
| LY2784544 (phase 1/2 study) | Scant literature | Scant literature | MF | Results pending | Results pending |
MF indicates myelofibrosis and includes PMF and post-PV/ET MF; DLT, dose-limiting toxicity; SIRS, systemic inflammatory response syndrome; and GI, gastrointestinal.