AP20187 (Synonyms: B/B Homodimerizer) |
Catalog No.GC14498
One-Click Copy Product Info
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AP20187 is a synthetic dimerizer compound that can induce the dimerization of proteins engineered to contain FKBP (FK506-binding protein) domains. AP20187 has been widely used in various biological research and therapeutic applications to control protein-protein interactions and regulate cellular processes.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 195514-80-8
Sample solution is provided at 25 µL, 10mM.
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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.
| 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 | |
| Synonyms | 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 | ||
| Formula | C82H107N5O20 | M.Wt | 1482.75 |
| Solubility | ≥ 74.1375mg/mL in DMSO, ≥ 50mg/ml in 75% ethanol aqueous solution | Storage | Store at -20°C,protect from light |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 674.4 μL | 3.3721 mL | 6.7442 mL |
| 5 mM | 134.9 μL | 674.4 μL | 1.3488 mL |
| 10 mM | 67.4 μL | 337.2 μL | 674.4 μL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 40 reference(s) in Google Scholar.)