Fedratinib hydrochloride hydrate (C09-1133-498)

Fedratinib hydrochloride hydrate (TG-101348 hydrochloride hydrate) is a potent, selective, ATP-competitive and orally active JAK2 inhibitor with IC 50 s of 3 nM for both JAK2 and JAK2V617F kinase . Fedratinib hydrochloride hydrate shows 35- and 334-fold selectivity over JAK1 and JAK3 , respectively. Fedratinib hydrochloride hydrate induces cancer cell apoptosis and has the potential for myeloproliferative disorders researchIn VitroFedratinib (TG101348) inhibits proliferation of a human erythroblast leukemia (HEL) cell line that harbors the JAK2V617F mutation, as well as a murine pro-B cell line expressing human JAK2V617F (Ba/F3 JAK2V617F), with an IC 50 value of approximately 300 nM for either line. Proliferation of parental Ba/F3 cells was inhibited to a comparable level, with an IC 50 value of ～420 nM. ?/nExposure of these cells to Fedratinib (TG101348) (0.1 μM, 0.3 μM, 1 μM, 3 μM, and 10 μM) reduces STAT5 phosphorylation at concentrations that parallel the concentrations required to inhibit cell proliferation. ?/nFedratinib (TG101348) (0.1 μM, 0.3 μM, 1 μM, 3 μM, and 10 μM) induces apoptosis in both HEL and Ba/F3 JAK2V617F cells in a dose-dependent manner. MCE has not independently confirmed the accuracy of these methods. They are for reference only.In VivoFedratinib (TG101348; 60-120 mg/kg; oral gavage; twice daily; for 42 days; C57Bl/6 mice) trewatment shows a dose-dependent reduction in polycythemia and a marked dose-dependent reduction in splenomegaly of treated animals . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: C57Bl/6 mice induced by the JAK2V617F mutation Dosage: 60 mg/kg, 120 mg/kg Administration: Oral gavage; twice daily; for 42 days Result: Showed a statistically significant reduction in hematocrit and leukocyte count, a dose-dependent reduction/elimination of extramedullary hematopoiesis.Form:SolidIC50& Target:JAK2 3 nM (IC 50 ) JAK2(V617F) 3 nM (IC 50 ) Flt3 15 nM (IC 50 ) Ret 48 nM (IC 50 ). Molecular Formula: C27H40Cl2N6O4S Molecular Weight: 615.6 PubChem CID: 67517580 Isomeric SMILES: CC1=CN=C(N=C1NC2=CC(=CC=C2)S(=O)(=O)NC(C)(C)C)NC3=CC=C(C=C3)OCCN4CCCC4.O.Cl.Cl