AP1903
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.
在竞争荧光偏振检测中,AP1903抑制F36V-FKBP,IC50值为5 nM。
AP1903是FKBP修饰配体的同型二聚体。在表达FKBP适当信号域融合蛋白的细胞或动物中,AP1903可用于触发信号传导。但是,由于配体与内源性FKBP的结合,该同型二聚体在体内的使用受到很大的局限性。
体外实验:在培养的人纤维肉瘤HT1080工程细胞中,AP1903选择性地抑制FKBP,从而有效地和剂量依赖地诱导细胞凋亡,EC50值约为0.1 nM [1]。
体内实验:在条件细胞消融的小鼠模型中,用不同剂量的AP1903处理细胞,血清hGH的水平被用于测量存活细胞的数量。结果表明,AP1903剂量依赖性的降低了血清hGH的水平,EC50值为0.4 mg/kg [1]。
临床实验:在静脉注射,单盲,安慰剂和盐水对照,递增剂量研究中,AP1903在所有剂量水平下都是安全的,耐受性良好,且在剂量远高于预期的治疗剂量下有很好的PK曲线[2]。
参考文献:
[1] Clackson T, Yang W, Rozamus LW, Hatada M, Amara JF, Rollins CT, Stevenson LF, Magari SR, Wood SA, Courage NL, Lu X, Cerasoli F Jr, Gilman M, Holt DA. Redesigning an FKBP-ligand interface to generate chemical dimerizers with novel specificity. Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10437-42.
[2] Iuliucci JD, Oliver SD, Morley S, Ward C, Ward J, Dalgarno D, Clackson T, Berger HJ. Intravenous safety and pharmacokinetics of a novel dimerizer drug, AP1903, in healthy volunteers. J Clin Pharmacol. 2001 Aug;41(8):870-9.
- 1. Sarah M Roelle, Nisha D Kamath, et al. "Mammalian Genomic Manipulation with Orthogonal Bxb1 DNA Recombinase Sites for the Functional Characterization of Protein Variants." ACS Synth Biol. 2023 Nov 17;12(11):3352-3365. PMID: 37922210
- 2. Regina J Lin, Janette Sutton, et al. "Constitutive Turbodomains enhance expansion and antitumor activity of allogeneic BCMA CAR T cells in preclinical models." Sci Adv. 2023 Aug 4;9(31):eadg8694. PMID: 37540748
- 3. Ariana Ghez Farrell, Bernadeta Dadonaite, et al. "Receptor-Binding Domain (RBD) Antibodies Contribute More to SARS-CoV-2 Neutralization When Target Cells Express High Levels of ACE2." bioRxiv. 2022 Aug 30;2022.08.29.505713. PMID: 36093349
- 4. Nidhi Shukla, Sarah M. Roelle, et al. "Mutants of human ACE2 differentially promote SARS-CoV and SARS-CoV-2 spike mediated infection." PLoS Pathog. 2021 Jul 16;17(7):e1009715. PMID: 34270613
- 5. Peng-Chieh Chen, Ya-Wen Hsueh, et al. "FGF primes angioblast formation by inducing ETV2 and LMO2 via FGFR1/BRAF/MEK/ERK." Cell Mol Life Sci 2020 Sep 10. PMID: 32910224
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 1411.63 |
Cas No. | 195514-63-7 |
Formula | C78H98N4O20 |
Solubility | ≥23.53 mg/mL in DMSO; insoluble in H2O; ≥56.2 mg/mL in EtOH |
SDF | Download SDF |
Canonical SMILES | O=C([C@@H](C(C=C1OC)=CC(OC)=C1OC)CC)N2[C@H](C(O[C@@H](C3=CC=CC(OCC(NCCNC(COC4=CC([C@H](CCC(C=C5OC)=CC=C5OC)OC([C@H]6N(C([C@@H](C(C=C7OC)=CC(OC)=C7OC)CC)=O)CCCC6)=O)=CC=C4)=O)=O)=C3)CCC(C=C8)=CC(OC)=C8OC)=O)CCCC2 |
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。 |
激酶实验 [1]: | |
FKBP结合实验 |
将亚饱和浓度的蛋白质与2.5 nM fluoro-FK506和竞争性配体的系列稀释物在Dynatech显微荧光板的孔中孵育30分钟。在Jolley FPM-2(Jolley Consulting and Research,Grayslake,IL)上读取偏振值。与不含竞争剂(100%)或不含蛋白质(0%)的对照相比,结合偏振的增加用作结合探针百分比的直接读数。通过使用四参数算法的非线性最小二乘法拟合确定导致50%探针置换(IC50)的竞争剂浓度。 |
细胞实验: [1] | |
细胞系 |
HT1080细胞系(ATCC CCL-121) |
制备方法 |
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℃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℃可放置数月。 |
反应条件 |
37℃ |
实验结果 |
在稳定表达包含肉豆蔻酰化序列、两个拷贝的F36V-FKBP和人Fas胞内结构域的融合蛋白的人纤维肉瘤系HT1080中,AP1903以剂量依赖性方式有效诱导凋亡性细胞死亡,EC50约为0.1 nM。 |
动物实验: [1] | |
动物模型 |
雄性nu/nu小鼠 |
给药剂量 |
静脉注射,0.01-100 mg/kg |
制备方法 |
以2 mL/kg配制在50%N,N-二甲基乙酰胺/ 50%(90% PEG-400/10%吐温80)中 |
实验结果 |
向雄性nu/nu小鼠注射表达组成型分泌hGH的Fas-F36V-FKBP构建体的HT1080细胞系。AP1903以剂量依赖性方式降低血清hGH水平,半数最大有效剂量为0.4±0.1 mg/kg。 |
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. Clackson T, Yang W, Rozamus LW et al. Redesigning an FKBP-ligand interface to generate chemical dimerizers with novel specificity. Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10437-42 |
质量控制和MSDS
- 批次: