AP20187
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
AP20187是一种小分子二聚体药物。
为了解决移植物对宿主的抵抗作用，需要对移植细胞的体内行为进行控制。在conditional system中，AP20187可作为二聚化（CID）的化学诱导剂。在基因治疗中，CIDs具有很大的优势，它可以在没有毒性作用的条件下获得选择性。体内研究表明，AP20187可以显著增加转导红细胞、血小板以及较小程度上粒细胞的数量。
据报道，AP20187也被用于AP20187–LFv2IRE系统。在该系统中，AP20187可引起LFv2IRE的激活，从而导致肝脏糖原含量和肌肉葡萄糖摄取的增加。
参考文献：
[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.
- 1. Loraine Kouba, Joël Bürgin, et al. "A composite, off-the-shelf osteoinductive material for large, vascularized bone flap prefabrication." Acta Biomater. 2022 Dec;154:641-649. PMID: 36261107
- 2. Adam L. Burrack, Zoe C. Schmiechen, et al. "Distinct myeloid antigen-presenting cells dictate differential fates of tumor-specific CD8+ T cells in pancreatic cancer." JCI Insight. 2022 Apr 8;7(7):e151593. PMID: 35393950
- 3. Colten Mitchell McEwan. "The Discovery of Novel 14-3-3 Binding Proteins ATG9A and PTOV1 and Their Role in Regulating Cancer Mechanisms." Brigham Young University. 2022.
- 4. Sébastien Pigeot, Thibaut Klein, et al. "Manufacturing of Human Tissues as off‐the‐Shelf Grafts Programmed to Induce Regeneration." Adv Mater. 2021 Oct;33(43):e2103737. PMID: 34486186
- 5. 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
- 6. 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
- 7. 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
- 8. 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
| Storage | Store at -20°C |
| M.Wt | 1482.75 |
| Cas No. | 195514-80-8 |
| Formula | C82H107N5O20 |
| Solubility | ≥74.14 mg/mL in DMSO; ≥100 mg/mL in EtOH |
| SDF | Download SDF |
| Canonical SMILES | O=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 | 蓝冰运输或根据您的需求运输。 |
| 一般建议 | 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。溶液形式一般不宜长期储存，请尽快用完。 |
| 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. | |
| 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 | ||||||
质量控制和MSDS
- 批次:
化学结构
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