AP20187
(Synonyms: B/B Homodimerizer) 目录号 : GC14498
AP20187是一种合成的二聚体化合物，能够诱导含有FKBP（FK506结合蛋白）结构域的蛋白质发生二聚化。AP20187在多种生物学研究和治疗中被用于控制蛋白质-蛋白质相互作用和调节细胞过程。
Cas No.:195514-80-8
Sample solution is provided at 25 µL, 10mM.
_1-3.$$$39978408@51.jpg');)
_1-9.$$$38538795@65.jpg');)
_1-9.$$$39112701@51.jpg');)
_1-7.$$$37316672@70.jpg');)
_366-372.$$$36198801@70.jpg');)
.$$$38565142@65.jpg');)
_1867-1883.$$$33248023@67.jpg');)
_eads6055.$$$39977546@45.jpg');)
_eadm9805.$$$40080571@45.jpg');)
_eadj3020.$$$39666821@45.jpg');)
_1-20.$$$39757301@28.jpg');)
_1-24.$$$38898113@28.jpg');)
_273-287.$$$36806353@46.jpg');)
_1-16.$$$37156877@44.jpg');)
_1-19.$$$37460805@44.jpg');)
_1291-1307.$$$34518654@46.jpg');)
AP20187 is a synthetic dimerizer compound that can induce the dimerization of proteins engineered to contain FKBP (FK506-binding protein) domains[1]. AP20187 has been widely used in various biological research and therapeutic applications to control protein-protein interactions and regulate cellular processes[2]. By binding to FKBP domains, AP20187 can bring two proteins together, thereby activating or modulating specific signaling pathways or cellular functions[3]. This mechanism allows for precise control over biological processes, making it a powerful tool for studying complex cellular mechanisms and developing targeted therapies. AP20187 has shown significant potential in both cancer biology and regenerative medicine[4].
In vitro, treatment of HeLa cells modified with the iCasp9 gene with AP20187 (0.025–2.5nM) increased cell death in a concentration-dependent manner. Moreover, repeated treatments led to the development of resistance to AP20187[5]. In PC12 cells expressing the inducible trkA (ItrkA) receptor, AP20187 (1pM to 1.25μM) significantly induced neurite outgrowth in a time- and dose-dependent manner. AP20187 treatment also increased the phosphorylation levels of Erk1/2 and Akt in ItrkA-transduced PC12 cells to levels comparable to those induced by 50μg/mL nerve growth factor (NGF). Additionally, AP20187 treatment significantly increased neurite outgrowth by 3–4 times[6].
In vivo, 25- to 29-month-old INK-ATTAC transgenic mice were treated with AP20187 (10mg/kg) via intraperitoneal injection, three times per week for 8 weeks. AP20187 treatment significantly reduced the number of p16Ink4a-positive microglia in the CA3 region of the hippocampus and decreased microglial activation and inflammatory cytokine expression. AP20187 also improved cognitive function in aged mice, reducing the time and errors required to complete maze tests[7]. In 5- to 6-month-old INK-ATTAC transgenic mice, AP20187 (3.3mg/kg) was administered via intraperitoneal injection, three times per week for 4 weeks (total dose 40mg/kg). AP20187 treatment significantly decreased p16Ink4a expression in renal tissue, reduced the expression of senescence-associated genes (Cdkn2a, Cdkn2d, Cdkn1a), and lowered levels of proinflammatory cytokines and matrix metalloproteinases. AP20187 also improved renal function by reducing plasma creatinine levels, increasing renal blood flow and glomerular filtration rate, and reducing renal fibrosis and inflammatory cell infiltration[8].
References:
[1] Xiao H, Wang LL, Shu CL, et al. Establishment of a cell model based on FKBP12 dimerization for screening of FK506-like neurotrophic small molecular compounds. J Biomol Screen. 2006 Apr;11(3):225-35.
[2] Baker DJ, Childs BG, Durik M, et al. Naturally occurring p16(Ink4a)-positive cells shorten healthy lifespan. Nature. 2016 Feb 11;530(7589):184-9.
[3] Baker DJ, Wijshake T, Tchkonia T, et al. Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature. 2011 Nov 2;479(7372):232-6.
[4] Pathak S, Singh V, Kumar N, et al. Inducible caspase 9-mediated suicide gene therapy using AAV6 vectors in a murine model of breast cancer. Mol Ther Methods Clin Dev. 2023 Nov 24;31:101166.
[5] Yuan Y, Ren H, Li Y, et al. Cell-to-cell variability in inducible Caspase9-mediated cell death. Cell Death Dis. 2022 Jan 10;13(1):34.
[6] Alfa RW, Tuszynski MH, Blesch A. A novel inducible tyrosine kinase receptor to regulate signal transduction and neurite outgrowth. J Neurosci Res. 2009 Sep;87(12):2624-31.
[7] Ogrodnik M, Evans SA, Fielder E, et al. Whole-body senescent cell clearance alleviates age-related brain inflammation and cognitive impairment in mice. Aging Cell. 2021 Feb;20(2):e13296.
[8] Kim SR, Puranik AS, Jiang K, et al. Progressive Cellular Senescence Mediates Renal Dysfunction in Ischemic Nephropathy. J Am Soc Nephrol. 2021 Aug;32(8):1987-2004.
AP20187是一种合成的二聚体化合物，能够诱导含有FKBP（FK506结合蛋白）结构域的蛋白质发生二聚化[1]。AP20187在多种生物学研究和治疗中被用于控制蛋白质-蛋白质相互作用和调节细胞过程[2]。通过与FKBP结构域结合，AP20187可以将两个蛋白质拉到一起，从而激活或调节特定的信号通路或细胞功能[3]。这种机制使得AP20187能够精确调控生物过程，成为研究复杂细胞机制和开发靶向治疗的强大工具。AP20187在癌症生物学和再生医学领域中研究中均显示出的潜力[4]。
在体外，AP20187（0.025-2.5nM）处理iCasp9基因修饰的HeLa细胞，HeLa细胞死亡率随AP20187浓度升高而增加，此外，多次给药处理导致细胞对AP20187产生耐药性[5]。AP20187（1pM至1.25μM）处理表达诱导型trkA（ItrkA）受体的PC12细胞，AP20187以时间和剂量依赖的方式显著诱导神经突起生长。AP20187处理导致ItrkA转导的PC12细胞中Erk1/2和Akt的磷酸化水平升高，与50μg/mL神经营养因子（NGF）处理相当。此外，AP20187处理显著增加了神经突起生长3-4倍[6]。
在体内，AP20187（10mg/kg）通过腹腔注射的方式对25-29个月大的INK-ATTAC转基因小鼠进行治疗，每周3天，连续治疗8周。AP20187处理显著减少了小鼠海马体CA3区域中p16Ink4a阳性的微胶质细胞数量，并降低了微胶质细胞的激活程度，减少了炎症因子的表达。AP20187处理还改善了老年小鼠的认知功能，减少了完成迷宫测试的时间和错误次数[7]。AP20187（3.3mg/kg）通过腹腔注射的方式对5-6个月大的INK-ATTAC转基因小鼠进行治疗，每周3次，连续治疗4周，总剂量为40mg/kg。AP20187处理显著降低了小鼠肾组织中p16Ink4a的表达，减少了衰老相关基因（Cdkn2a、Cdkn2d、Cdkn1a）的表达，并降低了促炎因子和基质金属蛋白酶的水平。AP20187还改善了肾功能，降低了血浆肌酐水平，提高了肾血流和肾小球滤过率，减少了肾纤维化和炎症细胞浸润[8]。
| Cell experiment [1]: | |
Cell lines | PC12 cells |
Preparation Method | PC12 cells were transduced with lentivirus containing the inducible trkA receptor (ItrkA) and GFP via an internal ribosome entry site (IRES). Cells were seeded into 12-well plates at a density of 5 × 103 cells/ml on collagen-coated plates and cultured in complete RPMI medium containing 10% horse serum and 5% fetal bovine serum. After 24 hours, the culture medium was switched to low serum medium (2% horse serum) for neurite outgrowth assays. Cells were treated with various concentrations of AP20187 (0.1pM to 1.25μM) in 0.1% ethanol for 72 hours. Control cells received only 0.1% ethanol. For time course experiments, neurite extension was monitored daily for 4 days, with medium changes every 2 days. |
Reaction Conditions | 0.1pM to 1.25μM; 72h |
Applications | AP20187 induced neurite outgrowth and differentiation in ItrkA-transduced PC12 cells in a time- and dose-dependent manner, with significant effects observed at concentrations as low as 1pM. |
| Animal experiment [2]: | |
Animal models | INK-ATTAC transgenic mice |
Preparation Method | Male, 5- to 6-months-old, INK-ATTAC mice underwent renal artery stenosis (RAS) or sham surgeries. Two weeks later, mice were randomized to receive AP20187 (AP) or vehicle. AP was delivered by intraperitoneal injections, three times a week, for 4 weeks (total 40mg/kg, 12 treatments). |
Dosage form | 3.3mg/kg, three times a week for 4 weeks (total 40mg/kg, 12 treatments); i.p. |
Applications | AP20187 selectively cleared cells highly expressing p16Ink4a, attenuated cellular senescence, and improved stenotic-kidney function. |
References: | |
| Cas No. | 195514-80-8 | SDF | |
| 别名 | B/B Homodimerizer | ||
| 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 | ||
| 分子式 | C82H107N5O20 | 分子量 | 1482.75 |
| 溶解度 | ≥ 74.1375mg/mL in DMSO, ≥ 50mg/ml in 75% ethanol aqueous solution | 储存条件 | Store at -20°C,protect from light |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
||
| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 0.6744 mL | 3.3721 mL | 6.7442 mL |
| 5 mM | 0.1349 mL | 0.6744 mL | 1.3488 mL |
| 10 mM | 0.0674 mL | 0.3372 mL | 0.6744 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet