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AZD1208

现货
Catalog No.
A3962
PIM激酶抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 770.00
现货
10mg
¥ 750.00
现货
25mg
¥ 1,600.00
现货
50mg
¥ 2,600.00
现货
200mg
¥ 6,500.00
现货

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Background

IC50: 0.4 nM for Pim-1, 5.0 nM for Pim-2, and 1.9 nM for Pim-3

Upregulation of Pim kinases has been observed in several types of leukemias and lymphomas. Pim-1, -2, and -3 promote cell proliferation and survival downstream of cytokine and growth factor signaling pathways. AZD1208 is a potent, highly selective, and orally available Pim kinase inhibitor.

In vitro: AZD1208 inhibited the growth of 5 of 14 acute myeloid leukemia (AML) cell lines tested. In MOLM-16 cells, AZD1208 also causes cell cycle arrest and apoptosis, accompanied by a dose-dependent reduction in phosphorylation of Bcl-2 antagonist of cell death [1].

In vivo: AZD1208 inhibits the growth of KG-1a and MOLM-16 xenograft tumors in vivo with a clear PK/PD relationship. Treatment with 10 mg/kg or 30 mg/kg of AZD1208 led to an 89% tumor growth inhibition or slight regression, respectively [1].

Clinical trials: AZD1208 is in Phase I trials evaluating the safety and tolerability profile and to determine the maximum tolerated dose (MTD). There are two ongoing trials where AZD1208 has been orally administered in AML and solid tumor (of all types) patients

Reference:
[1] Keeton EK, McEachern K, Dillman KS, Palakurthi S, Cao Y, Grondine MR, Kaur S, Wang S, Chen Y, Wu A, Shen M, Gibbons FD, Lamb ML, Zheng X, Stone RM, Deangelo DJ, Platanias LC, Dakin LA, Chen H, Lyne PD, Huszar D.   AZD1208, a potent and selective pan-Pim kinase inhibitor, demonstrates efficacy in preclinical models of acute myeloid leukemia. Blood. 2014;123(6):905-13.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt379.48
Cas No.1204144-28-4
FormulaC21H21N3O2S
SynonymsAZD 1208;AZD-1208
Solubility≥18.95 mg/mL in DMSO, <2.41 mg/mL in EtOH, <2.82 mg/mL in H2O
Chemical Name(5E)-5-[[2-[(3R)-3-aminopiperidin-1-yl]-3-phenylphenyl]methylidene]-1,3-thiazolidine-2,4-dione
SDFDownload SDF
Canonical SMILESC1CC(CN(C1)C2=C(C=CC=C2C=C3C(=O)NC(=O)S3)C4=CC=CC=C4)N
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验[1]:

细胞系

OCI-M1和EOL-1细胞系

溶解方法

在DMSO中的溶解度大于10 mM。为了获得更高的浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。

反应条件

9 h,1 μM

应用

AZD1208是一个高效的、高选择性和口服生物有效性的Pim激酶抑制剂,它可以有效抑制Pim-1,Pim-2和Pim-3的活性,Ki值分别为0.1 nM,1.92 nM和0.4 nM。AZD1208可抑制AML细胞的生长,诱导细胞凋亡和细胞周期阻滞。

动物实验[2]:

动物模型

SCID小鼠

剂量

口服给药,30-45 mg/kg

应用

AZD1208可以抑制c-MYC/Pim1转导的前列腺组织重组移植物、Myc-CaP同种异体移植物和人前列腺癌异种移植模型中肿瘤的形成。AZD1208通过抑制PIM,可减少c-MYC/Pim1移植物的生长和细胞增殖,增加细胞凋亡。此外,AZD1208也可以抑制多种原致癌基因通路,包括MYC通路和p53通路。

注意事项

请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。

References:

[1]. Keeton E K, McEachern K, Dillman K S, et al. AZD1208, a potent and selective pan-Pim kinase inhibitor, demonstrates efficacy in preclinical models of acute myeloid leukemia[J]. Blood, 2014, 123(6): 905-913.

[2]. Kirschner A N, Wang J, van der Meer R, et al. PIM kinase inhibitor AZD1208 for treatment of MYC-driven prostate cancer[J]. Journal of the National Cancer Institute, 2014, 107(2).

生物活性

Description AZD1208是一种有效的和可口服的Pim激酶抑制剂,对Pim1、Pim2和Pim3的IC50值分别为0.4 nM、5 nM和1.9 nM。
靶点 Pim1 Pim2 Pim3      
IC50 0.4 nM 1.9 nM 5 nM      

质量控制