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| Other Sizes |
Purity: ≥98%
| Targets |
AP20187 targets the FK506-binding protein (FKBP) family, specifically engineered fusion proteins containing the FKBPF36V domain. It functions as a homodimerizer, binding to two FKBP domains simultaneously and bringing them into close proximity. This induced proximity can activate chimeric receptors or signaling molecules, such as by dimerizing the intracellular domain of the Fas receptor to induce apoptosis, or by activating a chimeric insulin receptor to trigger insulin-like actions.
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| ln Vitro |
AP20187 (B/B Homodimerizer) (100 nM) treatment of LNCaP cells resulted in a considerable decrease in ro-iCaspase-9 levels and a significant weakening of caspase-9 processing activity [2].
In vitro, AP20187 (100 nM) has been shown to significantly reduce pro-caspase-9 levels and generate the smaller, processed active caspase-9 in LNCaP cells, indicating the induction of apoptosis. It potently inhibits the differentiation of transfected myoblasts in the absence of bFGF, blocks myotube formation and myosin heavy chain expression, and stimulates MAP kinase phosphorylation. AP20187 is also used to induce apoptosis in cells expressing FKBPF36V fusion proteins with the Fas receptor or FADD. |
| ln Vivo |
Real-time PCR analysis showed that AP20187 (B/B homodimer) (0.5 mg/kg, 2 mg/kg or 5 mg/kg) treatment significantly enhanced PLP/Fv2E-PERK in PID12 CHOP mRNA levels in the CNS of Fv2E. AP20187 therapy significantly decreased EAE-induced myelin damage during these procedures. AP20187 (B/B Homodimerizer) therapy dramatically reduced the number of degenerated axons and enhanced axonal density in PLP/Fv2E-PERK anatomical lumbar demyelinating lesions [2].
In vivo, AP20187 treatment has demonstrated significant biological effects. In PLP/Fv2E-PERK mice, administration at doses of 0.5, 2, or 5 mg/kg significantly increased CHOP mRNA levels in the central nervous system and alleviated EAE-induced myelin damage. It also significantly reduced the number of degenerating axons and increased axonal density in demyelinating lesions. In diabetic mice, AP20187-mediated activation of a chimeric insulin receptor resulted in insulin-like actions, increasing hepatic glycogen content and muscular glucose uptake. |
| Enzyme Assay |
The in vitro binding assay for AP20187 is typically performed using cell-free systems with purified FKBP domains. The interaction between AP20187 and FKBP can be studied using techniques such as surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC) to determine binding affinity and stoichiometry. Competition binding assays with fluorescently labeled FKBP can also be used to assess the compound's potency. These assays characterize the fundamental molecular interaction that underlies its dimerization activity.
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| Cell Assay |
In vitro cellular assays for AP20187 involve treating cells engineered to express FKBP-fusion proteins with the compound. Common readouts include the activation of specific signaling pathways (e.g., MAP kinase phosphorylation), changes in gene expression (e.g., CHOP mRNA), or the induction of apoptosis (e.g., caspase-9 activation). These assays are used to study signal transduction, protein function, and to validate the specificity of the dimerization system.
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| Animal Protocol |
In vivo animal studies for AP20187 are conducted in transgenic mouse models expressing FKBP-fusion proteins. AP20187 is typically administered systemically via injection. Endpoints include the analysis of target gene expression in tissues, assessment of disease pathology (e.g., myelin damage in EAE models), and evaluation of physiological effects like glucose uptake. These studies demonstrate the compound's utility for in vivo modulation of protein function.
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| ADME/Pharmacokinetics |
AP20187 is a cell-permeable small molecule that is typically administered via injection in vivo. As a synthetic compound, it is designed for research use and exhibits suitable pharmacokinetic properties for systemic administration. Its cell permeability allows it to reach intracellular FKBP fusion proteins. However, detailed pharmacokinetic parameters such as half-life, volume of distribution, and bioavailability are not extensively detailed in the available literature.
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| Toxicity/Toxicokinetics |
Specific toxicity data for AP20187 are not extensively detailed in the available literature. As a research tool, its toxicity profile is evaluated in the context of specific experimental models. The compound is generally well-tolerated at the doses used for inducing dimerization. However, comprehensive toxicological studies are not typically performed for research-use compounds. It is intended for research purposes only and is not for human use.
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| References |
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| Additional Infomation |
AP20187 is a tertiary amine compound with the structure 2-(aminomethyl)-N,N-dimethylpropane-1,3-diamine, wherein the primary amino groups are acylated by condensation with the carboxyl group of 2-{3-[(1R)-3-(3,4-dimethoxyphenyl)-1-hydroxypropyl]phenoxy}acetic acid, the hydroxyl group of which is esterified by condensation with the carboxyl group of L-piperidine acid, and the nitrogen atom of L-piperidine acid is acylated by condensation with (2S)-2-(3,4,5-trimethoxyphenyl)butyric acid. It is a synthetic, cell-membrane-permeable ligand used to induce homodimerization of fusion proteins containing the DmrB domain. It is an N-acylpiperidine, carboxylic acid ester, aromatic ether, and tertiary amine compound.
AP20187 is a widely used chemical inducer of dimerization (CID) in biomedical research, particularly for studies involving the FKBP system. It is a powerful tool for the conditional regulation of protein activity, allowing researchers to control signaling pathways, gene expression, and apoptosis with temporal precision. Its applications span diverse fields, including signal transduction, cancer research, and neuroscience. It is not approved for clinical use and is strictly a research reagent. |
| Molecular Formula |
C82H107N5O20
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| Molecular Weight |
1482.7485
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| Exact Mass |
1481.75
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| CAS # |
195514-80-8
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| PubChem CID |
78357784
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| Appearance |
White to yellow solid powder
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| LogP |
11.882
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
21
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| Rotatable Bond Count |
42
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| Heavy Atom Count |
107
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| Complexity |
2450
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| Defined Atom Stereocenter Count |
6
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| SMILES |
CC[C@@H](C1=CC(=C(C(=C1)OC)OC)OC)C(=O)N2CCCC[C@H]2C(=O)O[C@H](CCC3=CC(=C(C=C3)OC)OC)C4=CC(=CC=C4)OCC(=O)NCC(CNC(=O)COC5=CC=CC(=C5)[C@@H](CCC6=CC(=C(C=C6)OC)OC)OC(=O)[C@@H]7CCCCN7C(=O)[C@@H](CC)C8=CC(=C(C(=C8)OC)OC)OC)CN(C)C
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| InChi Key |
NSBGUMKAXUXKGI-BPNHAYRBSA-N
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| InChi Code |
InChI=1S/C82H107N5O20/c1-15-61(57-43-71(98-9)77(102-13)72(44-57)99-10)79(90)86-37-19-17-27-63(86)81(92)106-65(33-29-52-31-35-67(94-5)69(39-52)96-7)55-23-21-25-59(41-55)104-50-75(88)83-47-54(49-85(3)4)48-84-76(89)51-105-60-26-22-24-56(42-60)66(34-30-53-32-36-68(95-6)70(40-53)97-8)107-82(93)64-28-18-20-38-87(64)80(91)62(16-2)58-45-73(100-11)78(103-14)74(46-58)101-12/h21-26,31-32,35-36,39-46,54,61-66H,15-20,27-30,33-34,37-38,47-51H2,1-14H3,(H,83,88)(H,84,89)/t61-,62-,63-,64-,65+,66+/m0/s1
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| Chemical Name |
(1R,1'R)-(((((2-((dimethylamino)methyl)propane-1,3-diyl)bis(azanediyl))bis(2-oxoethane-2,1-diyl))bis(oxy))bis(3,1-phenylene))bis(3-(3,4-dimethoxyphenyl)propane-1,1-diyl)
(2S,2'S)-bis(1-((S)-2-(3,4,5-trimethoxyphenyl)butanoyl)piperidine-2-carboxylate)
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| Synonyms |
AP20187 AP-20187 AP 20187.
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
Ethanol : ~150 mg/mL (~101.16 mM)
DMSO : ≥ 57 mg/mL (~38.44 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 6 mg/mL (4.05 mM) in 10% EtOH + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 60.0 mg/mL clear EtOH stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 6 mg/mL (4.05 mM) in 10% EtOH + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 60.0 mg/mL clear EtOH stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (1.69 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: ≥ 2.5 mg/mL (1.69 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL corn oil and mix evenly. Solubility in Formulation 5: 2.4 mg/mL (1.62 mM) in 4% ethanol 10% PEG-400 2% Tween80 + 84%water. (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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