1354799-87-3
1354799-87-3 結(jié)構(gòu)式
基本信息
JAK2抑制劑(NS-018 MALEATE)
Ilginatinib maleate
NS018 MALEATE
ILGINATINIB MALEATE
ILGINATINIB (MALEATE) (NS-018 (MALEATE))
物理化學(xué)性質(zhì)
常見問(wèn)題列表
|
JAK2 0.72 nM (IC 50 ) |
Tyk2 22 nM (IC 50 ) |
JAK1 33 nM (IC 50 ) |
JAK3 39 nM (IC 50 ) |
Ilginatinib maleate (NS-018 maleate) is a highly active JAK2 inhibitor, with an IC
50
of 0.72 nM, 46-, 54-, and 31-fold selectivity for JAK2 over JAK1 (IC
50
, 33 nM), JAK3 (IC
50
, 39 nM), and Tyk2 (IC
50
, 22 nM). Ilginatinib maleate also inhibits Src-family kinases, especially SRC and FYN, and weakly inhibits ABL and FLT3 with 45- and 90-fold selectivity for JAK2, respectively. Ilginatinib maleate shows potent inhibitory activity against cell lines JAK2V617F or MPLW515L mutations or the TEL-JAK2 fusion gene (expressing a constitutively activated JAK2) with IC
50
of 11-120?nM, but has only minimal cytotoxicity against most other hematopoietic cell lines that have no constitutively activated JAK2.
Ilginatinib maleate (0.5 μM) preferentially suppresses colony-forming unitgranulocyte/macrophage (CFU-GM) formation from myelodysplastic syndrome (MDS)-derived bone marrow mononuclear cells (BMMNCs). Ilginatinib maleate (1 μM) suppresses the phosphorylation of STAT3 (the downstream kinase of JAK2) in CFU-GM-forming cells from MDS patients.
Ilginatinib maleate (NS-018 maleate) (12.5, 25, 50, 100 mg/kg, p.o.) potently prolongs the survival of mice and reduces splenomegaly in a mouse Ba/F3-JAK2V617F disease model.
Ilginatinib maleate (25, 50 mg/kg, p.o.) significantly reduces leukocytosis, hepatosplenomegaly and extramedullary hematopoiesis, improves nutritional status, and prolongs survival in JAK2V617F transgenic mice.