| 名称 | NVP-BSK805 2HCl (1092499-93-8(free base)) |
| 描述 | NVP-BSK805 2HCl (1092499-93-8(free base)) (BSK 805)(IC50=0.5 nM), a specific and effective ATP-competitive JAK2 inhibitor, is more than 20-fold specificity over JAK1, JAK3 and TYK2. |
| 细胞实验 | The anti-proliferative activity of JAK2 inhibitors is determined by incubating cells for 72 hours with an 8-point concentration range of compound and cell proliferation relative to DMSO-treated cells is measured using the colorimetric WST-1 (Roche Diagnostics GmbH) cell viability readout. Of each triplicate treatment, the mean is calculated and these data are plotted in XLfit 4 (ID Business Solutions, Ltd.) to determine the half-maximal growth inhibition (GI50) values.(Only for Reference) |
| 体外活性 | NVP-BSK805 is found to potently inhibit JAK2, whereas displaying more than 20-fold selectivity towards JAK1, JAK3, and TYK2. NVP-BSK805 causes half-maximal inhibition of full-length JAK2V617F and JAK2 wild-type enzymes at 0.5 nM. NVP-BSK805 blocks the growth of JAK2V617F cells (Ba/F3) and induces apoptosis with a GI50 at concentrations ＜100 nM. As constitutive STAT5 phosphorylation in dependent on JAK2, NVP-BSK805 is found to potently suppress STAT5 phophorylation at ≥ 100 nM concentrations in the JAK2 V617F -mutant cell lines, like MB-02. Incubation of SET-2 cells with 150 nM and 1 μM of NVP-BSK805, which corresponds to concentration yielding 75% and 95% growth inhibition, respectively, for 24, 48, and 72 hours lead to concentration- and time- dependent induction of apoptosis. These results are evidenced by the detection of cleaved PARP, reduced Bcl-xL expression, and a strong increase in the number of cells with less than 2N DNA content. [1] NVP-BSK805 triggered cell death requires activation of caspase cascades and is overcome by caspase inhibition in both SET-2 and MB-02 cells. NVP-BSK805 modulates the post-translational modification of Bim and levels of Mcl-1 in JAK2V617F cells, SET-2 and MB-02 cells. [2] |
| 体内活性 | Oral bioavailability of NVP-BSK805 in mice is estimated to be 45%, while it is 50% in rats. Oral administration of NVP-BSK805 at 150 mg/kg suppresses STAT5 phosphorylation, splenomegaly, and leukemic cell spreading in a Ba/F3 JAK2V617F cell–driven mouse model. NVP-BSK805 suppresses rhEpo-induced STAT5 phosphorylation as well as rhEpo-mediated polycythemia and splenomegaly in BALB/c mice at doses of 25, 50, and 100 mg/kg orally. [1] |
| 存储条件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature. |
| 溶解度 | H2O : 3 mg/mL (5.32 mM), Sonication is recommended.
DMSO : 113 mg/mL (200.54 mM), Sonication is recommended.
Ethanol : 15 mg/mL (26.62 mM), Sonication is recommended.
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| 关键字 | 盐酸NVP-BSK805 | TyrosineKinases | Tyrosine Kinases | Tyk2 | NVP-BSK805 2HCl (1092499-93-8 free base) | NVP-BSK-805 Dihydrochloride | NVP-BSK805 Dihydrochloride | NVP-BSK805 2HCl (1092499-93-8(free base)) | NVP-BSK-805 2HCl (1092499-93-8(free base)) | NVPBSK805 2HCl (1092499938(free base)) | NVP-BSK-805 | NVP-BSK805 | NVP-BSK 805 Dihydrochloride | NVP-BSK 805 | NVP BSK805 2HCl (1092499 93 8(free base)) | JAK3 | JAK2 | JAK1 | BSK-805 | BSK805 |
| 相关产品 | JAK-IN-10 | Fedratinib | Tofacitinib Citrate | Deucravacitinib | Gefitinib | RO8191 | TAK-901 | CEP-33779 | GSK 3 Inhibitor IX | Ruxolitinib phosphate | Delgocitinib | Ibrutinib |
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