| 货号 (SKU) | 包装规格 | 是否现货 | 价格 | 数量 |
|---|---|---|---|---|
| K407735-1ml |
1ml |
现货  |
|
| 英文别名 | (E)-(4-(2-(1H-indazol-3-yl)vinyl)phenyl)(piperazin-1-yl)methanone |
|---|---|
| 规格或纯度 | Moligand™, 10mM in DMSO |
| 英文名称 | KW-2449 |
| 生化机理 | KW-2449 是一种多靶点抑制剂，主要针对 Flt3，IC50 为 6.6 nM，对 FGFR1、Bcr-Abl 和 Aurora A 有一定作用；对 PDGFRβ、IGF-1R 和 EGFR 影响很小。第 1 阶段。 |
| 储存温度 | -80℃储存 |
| 运输条件 | 超低温冰袋运输 |
| 作用类型 | 抑制剂 |
| 作用机制 | 酪氨酸蛋白激酶 ABL 抑制剂 |
| 产品介绍 |
KW-2449能较强地抑制Flt3，IC50为6.6 nM，对FGFR1，Bcr-Abl和Aurora A的抑制性适中，而对 PDGFRβ，IGF-1R，EGFR则无抑制性。A multikinase inhibitor of FLT3, ABL, ABL-T315I, and Aurora kinase。 Information KW-2449 is a multiple-targeted inhibitor, mostly forFlt3withIC50of 6.6 nM, modestly potent to FGFR1, Bcr-Abl and Aurora A; little effect on PDGFRβ, IGF-1R, EGFR. Phase 1. KW-2449, a multikinase inhibitor of FLT3, ABL, ABL-T315I, and Aurora kinase, is under investigation to treat leukemia patients. KW-2449 shows the potent growth inhibitory effects on leukemia cells with FLT3 mutations by inhibition of the FLT3 kinase, resulting in the down-regulation of phosphorylated-FLT3/STAT5, G1 arrest, and apoptosis. Oral administration of KW-2449 shows dose-dependent and significant tumor growth inhibition in FLT3-mutated xenograft model with minimum bone marrow suppression. In FLT3 wild-type human leukemia, KW-2449 induces the reduction of phosphorylated histone H3, G2/M arrest, and apoptosis. In Imatinib-resistant leukemia, KW-2449 contributes to release of the resistance by the simultaneous down-regulation of BCR/ABL and Aurora kinases. The inhibitory activity of KW-2449 is not affected by the presence of human plasma protein, such as α1-acid glycoprotein. KW-2449 has potent growth inhibitory activity against various types of leukemia by several mechanisms of action. KW-2449 has significant activity and warrants clinical study in leukemia patients with FLT3 mutations as well as Imatinib-resistant mutations. Phosphorylation levels of FLT3 and STAT5 are decreased by KW-2449 in a dose-dependent manner. In addition, it potently inhibits ABL-T315I, which is associated with IM resistance, with IC50 of 4 nM. On the other hand, KW-2449 has little effect on PDGFRβ, IGF-1R, EGFR, and various serine/threonine kinases even at a concentration of 1 μM. KW-2449 has the potent growth inhibitory activities against not only FLT3/ITD-expressing leukemia cells but also FLT3/KDM-activated and wild-type FLT3-overexpressing leukemia cells. In accordance with growth inhibitory effect, KW-2449 suppresses the phosphorylations of FLT3 (P-FLT3) and its downstream molecule phospho-STAT5 (P-STAT5) in MOLM-13 cells in a dose-dependent manner. Furthermore, KW-2449 increases the percentage of cells in the G1 phase of the cell cycle and reciprocally reduces the percentage of cells in the S phase, resulting in the increase of apoptotic cell population. KW-2449 can dephosphorylate constitutively active WT-FLT3 kinase but not inhibit the proliferation of leukemia cells if they are not mainly addicted to FLT3 the kinase. KW-2449 is rapidly absorbed and converted to a major metabolite M1.Preclinical studies reveal that KW-2449 is converted by monoamine oxidase-B (MAO-B) and aldehyde oxidase into its major metabolite M1.KW-2449 mediates cytotoxicity thru inhibition of FLT3/ITD.KW-2449 is a direct inhibitor of FLT3 and induces inhibition of its downstream target STAT5. KW2449 interacts synergistically with HDACIs to induce apoptosis in Ph+ CML cells in a time- and concentration-dependent manner. KW2449 synergistically enhances the lethality of vorinostat/SNDX275 in CML cells.KW-2449 regimens are active against additional IM-resistant Bcr/Abl+ leukemia cells. KW2449 moderately reduces phosphorylation of histone H3, an indicator of Aurora B activity, in nocodozole-treated K562 cells. In vivo In the MOLM-13 tumor xenograft model, oral administration of KW-2449 for 14 days shows a potent and significant antitumor effect in a dose-dependent manner. cell lines： Concentrations：33nM, 75nM, 0.1μM, 0.3μM and 0.15μM Incubation Time：24, 48, and 72 hours Powder Purity:≥99% |
| 分子类型 | 小分子 |
|---|---|
| Isomeric SMILES | C1CN(CCN1)C(=O)C2=CC=C(C=C2)/C=C/C3=NNC4=CC=CC=C43 |
| 分子量 | 332.4 |
| Reaxy-Rn | 18931699 |
| Reaxys-RN link address | https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=18931699&ln= |
| 溶解性 | Solubility (25°C) In vitro DMSO: 47 mg/mL (198.92 mM); Ethanol: 3 mg/mL (12.69 mM); Water: Insoluble; |
|---|
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