计算溶液所需的质量、体积或浓度。
| 活性类型 | 活性值-log(M) | 作用机制 | 期刊 | 参考文献(PubMed IDs) |
|---|
KW-2449, 酪氨酸蛋白激酶 ABL 抑制剂
有货
为什么选择此级别
Moligand™ 级 ，适用于对基线干扰要求严格的色谱和分析工作流程。
储存与运输
-80℃储存。特低温运输 。请查阅批次 COA 获取详细规格。
质量文档
SDS、COA、产品数据表及规格说明书均可下载。可通过批号查询获取批次 COA。
文献证明
在色谱分析、有机合成和交叉偶联反应领域已被 0 篇同行评审文献引用。
概述
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.
In vitro
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 Data
cell lines：
Concentrations：33nM, 75nM, 0.1μM, 0.3μM and 0.15μM
Incubation Time：24, 48, and 72 hours
Powder Purity:≥99%
规格
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。
储存条件
-80℃储存
运输条件
特低温运输
作用类型
抑制剂
作用机制
酪氨酸蛋白激酶 ABL 抑制剂
名称和识别符
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=
技术文档
高级数据
关联靶点（人）
SRPK2
Tchem
SRSF 蛋白激酶 2(SRSF protein kinase 2)
(1 活性数据)
STK17A
Tchem
丝氨酸/苏氨酸蛋白激酶 17A(Serine/threonine-protein kinase 17A)
(1 活性数据)
STK10
Tchem
丝氨酸/苏氨酸蛋白激酶10(Serine/threonine-protein kinase 10)
(1 活性数据)
STK16
Tchem
丝氨酸/苏氨酸蛋白激酶 16(Serine/threonine-protein kinase 16)
(1 活性数据)
STK17B
Tchem
丝氨酸/苏氨酸蛋白激酶 17B(Serine/threonine-protein kinase 17B)
(1 活性数据)
YES1
Tclin
酪氨酸蛋白激酶 是(Tyrosine-protein kinase Yes)
(1 活性数据)
FLT3
Tclin
受体型酪氨酸蛋白激酶 FLT3(Receptor-type tyrosine-protein kinase FLT3)
(12 活性数据)
TNIK
Tchem
TRAF2 与 NCK 相互作用蛋白激酶(TRAF2 and NCK-interacting protein kinase)
(1 活性数据)
SLK
Tchem
STE20 类丝氨酸/苏氨酸蛋白激酶(STE20-like serine/threonine-protein kinase)
(1 活性数据)
PLK4
Tchem
丝氨酸/苏氨酸蛋白激酶 PLK4(Serine/threonine-protein kinase PLK4)
(1 活性数据)
MINK1
Tchem
畸形类激酶1(Misshapen-like kinase 1)
(1 活性数据)
MAP4K2
Tchem
丝裂原活化蛋白激酶激酶激酶2(Mitogen-activated protein kinase kinase kinase kinase 2)
(1 活性数据)
MAP3K19
Tchem
丝裂原活化蛋白激酶激酶激酶19(Mitogen-activated protein kinase kinase kinase 19)
(1 活性数据)
BMP2K
Tchem
BMP-2诱导蛋白激酶(BMP-2-inducible protein kinase)
(1 活性数据)
AURKA
Tchem
极光激酶A(Aurora kinase A)
(1 活性数据)
AURKB
Tchem
极光激酶B(Aurora kinase B)
(1 活性数据)
Tchem
未表征蛋白 FLJ45252(Uncharacterized protein FLJ45252)
(1 活性数据)
ABL1
Tclin
酪氨酸蛋白激酶ABL1(Tyrosine-protein kinase ABL1)
(7 活性数据)
KIT
Tclin
肥大细胞/干细胞生长因子受体试剂盒(Mast/stem cell growth factor receptor Kit)
(3 活性数据)
PAK2
Tchem
丝氨酸/苏氨酸蛋白激酶 PAK 2(Serine/threonine-protein kinase PAK 2)
(1 活性数据)
OLA1
Tchem
Obg类ATP酶1(Obg-like ATPase 1)
(1 活性数据)
MYLK3
Tchem
肌球蛋白轻链激酶 3(Myosin light chain kinase 3)
(1 活性数据)
化学和物理性质
溶解性
Solubility (25°C) In vitro DMSO: 47 mg/mL (198.92 mM); Ethanol: 3 mg/mL (12.69 mM); Water: Insoluble;
质检证书（CoA,COO,BSE/TSE 和分析图谱)
C of A & Other Certificates(BSE/TSE, COO):
输入批号以搜索分析图谱:
溶液计算器
常见问题
「Moligand?」是什么？
「Moligand?」是阿拉丁科学的高端产品线之一，专为多个工作流程中的高纯度应用而设计。与同类工作流程中的标准级别相比，「Moligand?」产品通常具有更严格的规格、更严谨的 QC 以及更强的批间一致性。
本产品应如何储存？
请于?80 °C条件下保存。需超低温保存以维持规定的有效期。
本产品如何运输？
本产品采用干冰配冷袋冷冻运输。收货后请立即拆包，并按上述储存条件保存；处理干冰时请戴隔热手套并保持通风。
本产品的 CAS 号、分子式和分子量是多少？
本产品的 CAS 号为 1000669-72-6，分子式为 C20H20N4O，分子量为 332.4 g/mol。
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