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BAY 80-6946 (Copanlisib)

现货
Catalog No.
B2178
PI3K抑制剂
组合的产品项目
规格价格库存 数量
5mg
¥ 1,680.00
现货
10mg
¥ 2,730.00
现货
50mg
¥ 6,180.00
现货

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Background

Several phosphatidylinositol-3-kinase (PI3K) inhibitors are being investigated as a treatment for patients with B-cell malignancies. Such agents prevent activation of PI3K enzymes that are hyperactive in many B-cell malignancies and associated with tumor progression. Copanlisib is a novel pan-Class I phosphatidylinositol-3-kinase (PI3K) inhibitor with potent preclinical inhibitory activity against both PI3K-d and PI3K-α isoforms.
In vitro: BAY 80-6946 is a phosphoinositide 3-kinase (PI3K) inhibitor with potential antineoplastic activity, which inhibits proliferation with IC50 of 147 nM in HuCCT-1 (KRASG12D ) and 137 nM in EGI-1 (KRASG12D ) cell lines [1].
In vivo: BAY 80-6946 is generally well tolerated through the maximum tolerated dose (MTD) of 0.8 mg/kg. pharmacokinetics (PK) results support dosing weekly. Grade 2 or 3 hyperglycemia in the first 24 hrs after receiving a MTD dose. Pharmacokinetics, clinical SD as well as FDG-PET data are consistent with effective exposure and PI3K pathway inhibition. [2].
Clinical trial: Copanlisib (BAY 80-6946), developed by Bayer, is a selective Class I phosphoinositide 3-kinase inhibitor which has shown promise in Phase I/II clinical trials for the treatment of non-Hodgkin lymphoma and chronic lymphocytic leukemia. Phase II study shows that Copanlisib is active as a single-agent in heavily pretreated, advanced refractory/relapsed FL, MZL, , CLL and SLL. Copanlisib exhibited an acceptable toxicity profile, which was consistent with previous findings (https://ash.confex.com/ash/2014/webprogram/Paper70672.html).
References:
[1] Patnaik A, et al. J Clin Oncol, 29, 2011, (suppl, abstr 3035)
[2] Andrea H, et al. Cancer Res, 2012; 72(8), (suppl, Abstract 869)

文献引用

1. Almohazey D, Lo YH, et al. "The ErbB3 receptor tyrosine kinase negatively regulates Paneth cells by PI3K-dependent suppression of Atoh1." Cell Death Differ. 2017 May;24(5):855-865. PMID:28304405

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt480.52
Cas No.1032568-63-0
FormulaC23H28N8O4
Solubility<0.96mg/mL in DMSO, <1.022mg/mL in H2O
Chemical Name2-amino-N-[7-methoxy-8-(3-morpholin-4-ylpropoxy)-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl]pyrimidine-5-carboxamide
SDFDownload SDF
Canonical SMILESCOC1=C(C=CC2=C1N=C(N3C2=NCC3)NC(=O)C4=CN=C(N=C4)N)OCCCN5CCOCC5
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

激酶实验 [1]:

生化脂质激酶测定

在包被2 μg/well磷脂酰肌醇 (PI) 和磷脂酰丝氨酸 (PS)(1:1摩尔比)的384孔MaxiSorp板中,测定BAY 80-6946对33P渗进PI的抑制作用,从而评估BAY 80-6946对PI3Kα、PI3Kβ和 PI3Kγ的作用。在每种PI3K亚型实验中,使用9 μL反应缓冲液(50 mM MOPSO,pH 7.0,100 mM NaCl,4 mM MgCl2,0.1% BSA)。上述反应缓冲液含7.5 ng His标记的N末端截短的p110α或p110β蛋白,或25 ng纯化的人p110γ蛋白。加入5 μL含有20 μCi/mL [γ-33P]-ATP的40 μM ATP溶液开始反应。在室温下孵育2小时后,加入5 μL 25 mM EDTA溶液终止反应。将板冲洗后,加入Ultima Gold闪烁混合物 (25 μL)。使用BetaPlate液体闪烁计数器测定掺入到固定PI底物中的放射性物质。

细胞实验 [1]:

细胞系

一组癌细胞系

制备方法

该化合物在DMSO中的溶解度有限。若配制更高浓度的溶液,一般步骤如下:请将试管置于37 °C加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20 °C可放置数月。

反应条件

5 μM;72小时

实验结果

在一组PI3K信号持续激活的癌细胞系中,BAY 80-6946显著抑制细胞增殖。某些乳腺癌细胞、子宫内膜癌细胞以及血液肿瘤细胞对BAY 80-6946非常敏感(IC50值 < 10 nM)。

动物实验 [1]:

动物模型

大鼠KPL4肿瘤异种移植模型

给药剂量

0.5 ~ 6 mg/kg;静脉注射;从肿瘤细胞移植后的第14天开始给药,每隔2天给1次药,一共给5次

实验结果

在第25天(即最后1次给药后的第3天),0.5 mg/kg、1 mg/kg、3 mg/kg和6 mg/kg BAY 80-6946分别具有77%、84%、99%和100%的肿瘤生长抑制(TGI)率。此外,在3 mg/kg和6 mg/kg剂量下,BAY 80-6946导致完全的肿瘤消退。

注意事项

请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。

References:

[1]. Liu N, Rowley BR, Bull CO, Schneider C, Haegebarth A, Schatz CA, Fracasso PR, Wilkie DP, Hentemann M, Wilhelm SM, Scott WJ, Mumberg D, Ziegelbauer K. BAY 80-6946 is a highly selective intravenous PI3K inhibitor with potent p110α and p110δ activities in tumor cell lines and xenograft models. Mol Cancer Ther. 2013 Nov;12(11):2319-30.

质量控制

化学结构

BAY 80-6946 (Copanlisib)

相关生物数据

BAY 80-6946 (Copanlisib)