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AP20187

现货
Catalog No.
B1274
二聚体药,具有细胞通透性。
组合的产品项目
规格价格库存 数量
1mg
¥ 3,300.00
现货
5mg
¥ 8,800.00
现货
10mg
¥ 13,000.00
现货
50mg
¥ 26,000.00
现货

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Background

AP20187 is a small dimerizer drug [1].

To solve the graft-versus-host disease, the in vivo behavior of the transplanted cells should be controlled. AP20187 is used in the conditional system as a chemical inducer of dimerization (CID). Another component is a fusion protein. The CIDs have advantages in gene therapy, it offers the possibility of achieving selection without the toxic effects. In vivo studies show that AP20187 can produces a notable expansion of transduced red cells, platelets, and to a lesser extent, granulocytes [1].

AP20187 is also reported to be used in an AP20187–LFv2IRE system. In this system, AP20187 administration causes the activation of LFv2IRE and results in increased uptake of both hepatic glycogen content and muscular glucose [2].

References:
[1] Neff T, Blau CA. Pharmacologically regulated cell therapy. Blood. 2001 May 1;97(9):2535-40.
[2] Cotugno G, Formisano P, Giacco F, Colella P, Beguinot F, Auricchio A. AP20187-mediated activation of a chimeric insulin receptor results in insulin-like actions in skeletal muscle and liver of diabetic mice. Hum Gene Ther. 2007 Feb;18(2):106-17.

文献引用

1. Bougioukli S, Vakhshori V, et al. "Regulated ex vivo regional gene therapy for bone repair using an inducible caspase-9 suicide gene system." Gene Ther. 2019 Jun;26(6):230-239. PMID:30962534
2. Wakahashi K, Minagawa K, et al. "Vitamin D receptor-mediated skewed differentiation of macrophages initiates myelofibrosis and subsequent osteosclerosis." Blood. 2019 Feb 4. pii: blood-2018-09-876615. PMID:30718230
3. Jacobs CL, Badiee RK, Lin MZ. "StaPLs: versatile genetically encoded modules for engineering drug-inducible proteins." Nat Methods. 2018 Jul;15(7):523-526. PMID:29967496
4. Miyake M, Kuroda M, et al. "Ligand-induced rapid skeletal muscle atrophy in HSA-Fv2E-PERK transgenic mice." PLoS One. 2017 Jun 23;12(6):e0179955. PMID:28644884

Chemical Properties

StorageStore at -20°C
M.Wt1482.75
Cas No.195514-80-8
FormulaC82H107N5O20
Solubility≥74.1375mg/mL in DMSO, ≥50mg/ml in 75% ethanol aqueous solution
SDFDownload SDF
Canonical SMILESO=C([C@@H]1CCCCN1C([C@@H](CC)C2=CC(OC)=C(OC)C(OC)=C2)=O)O[C@H](CCC3=CC(OC)=C(OC)C=C3)C4=CC=CC(OCC(NCC(CNC(COC5=CC=CC([C@@H](CCC6=CC(OC)=C(OC)C=C6)OC([C@H]7N(C([C@@H](CC)C8=CC(OC)=C(OC)C(OC)=C8)=O)CCCC7)=O)=C5)=O)CN(C)C)=O)=C4
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

CHO-AA8-Tet off细胞

溶解方法

在DMSO中的溶解度>74.1mg/mL。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。

应用

MLL-AF9融合蛋白cDNA一式三份转染CHO细胞,连同一个Myc E box HSV TK荧光素酶报告质粒和一个CMV驱动的Renilla荧光素酶对照质粒。结果用标准化的萤火虫萤光素酶活性与转染MSCV新霉素对照载体的活性的比值表示。在二聚化因子AP20187存在时,转染MLL-FKBP的细胞对Myc E box HSV TK报告基因具有强烈的和剂量依赖的转录激活活性。融合蛋白的二聚化具有将近250倍的转录激活活性。

动物实验[2]:

动物模型

CD1小鼠

剂量

10 mg/kg,腹腔注射。

溶解方法

为了评估LFv2IRE的表达和酪氨酸磷酸化,在注射AP20187之前的4周,CD1小鼠经尾静脉注射AAV2/8-TBG-LFv2IRE或AAV2/1-MCK-LFv2IRE载体。在AP20187给药后2小时,AP20187依赖性的LFv2IRE酪氨酸磷酸化被检测到,在6小时之后达到峰值,24小时后回到基础水平。在接受AAV2/8-TBG-LFv2IRE而没有AP20187刺激的小鼠肝脏样品中检测到低水平的基础LFv2IRE磷酸化水平,表明该系统的最小泄漏。

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] Martin M E, Milne T A, Bloyer S, et al. Dimerization of MLL fusion proteins immortalizes hematopoietic cells. Cancer cell, 2003, 4(3): 197-207.

[2] Cotugno G, Formisano P, Giacco F, et al. AP20187-mediated activation of a chimeric insulin receptor results in insulin-like actions in skeletal muscle and liver of diabetic mice. Human gene therapy, 2007, 18(2): 106-117.

生物活性

描述 AP20187是一种合成的细胞通透性药物,可以二聚化并激活包含生长因子受体信号传导域的融合蛋白。
靶点 fusion proteins containing a growth factor receptor signaling domain          
IC50            

质量控制

化学结构

AP20187

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