| Size | Price | Stock | Qty |
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| Targets |
The compound specifically binds to FKBP12 (FK506-binding protein 12), particularly the F36V mutant variant engineered for orthogonal control in PROTAC applications. AP1867 acts as a high-affinity synthetic ligand for FKBP, and the (Methoxyethylamine) derivative contains an aminoethoxy group that provides a stable linkage point, enabling its use as a warhead for recruiting FKBP12 proteins to E3 ubiquitin ligases.
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| ln Vitro |
The compound itself is an FKBP ligand rather than a direct enzyme inhibitor; its primary activity is its high-affinity binding to FKBP12 (Kd typically in the low nanomolar range). As a building block, its cellular activity is demonstrated through successful PROTAC-mediated degradation of FKBP12 fusion proteins when incorporated into complete PROTAC molecules. The AP1867-FKBP12 interaction has been extensively validated as one of the most selective protein-ligand pairs for inducible systems.
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| ln Vivo |
Specific in vivo data for this building block alone are not available, as it is not administered as a therapeutic drug itself. When incorporated into a PROTAC molecule, the resulting FKBP12-targeting degrader demonstrates in vivo activity. AP1867-based PROTACs have been successfully used in mouse models to achieve FKBP12 degradation, validating the utility of this ligand scaffold for in vivo chemical biology applications.
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| Enzyme Assay |
The binding affinity and selectivity of AP1867-based ligands are typically assessed using surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC). Recombinant FKBP12 protein is immobilized on a sensor chip or placed in a reaction cell. Varying concentrations of AP1867-3-(Methoxyethylamine) are flowed over the surface or titrated, and binding kinetics and dissociation constants (Kd) are calculated from the resulting sensorgrams or thermograms.
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| Cell Assay |
While the building block itself is not directly used in cellular assays, the completed PROTAC containing this FKBP ligand is used for degrader studies. Target cells expressing FKBP12-fused proteins are treated with PROTACs incorporating AP1867-3-(Methoxyethylamine). After 4-24 hours of treatment, cells are lysed and FKBP12 fusion protein levels are assessed by Western blot using an anti-FKBP12 or protein-specific antibody, alongside negative controls lacking the ligand or E3 ligase ligand.
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| Animal Protocol |
In vivo studies are conducted using complete PROTAC molecules assembled with this FKBP ligand, not the building block alone. In a typical study, mice bearing xenograft tumors expressing FKBP12-fused target proteins are administered the PROTAC via intraperitoneal or intravenous injection at doses such as 10-30 mg/kg. Tumor tissues and other organs are harvested after treatment for Western blot analysis of FKBP12 target protein levels to evaluate degradation efficacy and biodistribution.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties are determined for the final PROTAC molecule rather than for this ligand alone. As a small molecule with molecular weight 678.81 g/mol and predicted LogP 5.8, the AP1867 building block is highly lipophilic and likely has good membrane permeability. It is intended for conjugation rather than direct in vivo administration, and its solubility in DMSO (~240 mg/mL) makes it suitable for further chemical derivatization.
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| Toxicity/Toxicokinetics |
Toxicological data are not available for AP1867-3-(Methoxyethylamine) as a stand-alone compound, as it is a research building block used exclusively for chemical synthesis. When incorporated into PROTACs, overall toxicity is evaluated for the complete degrader molecule. The FKBP12 ligand itself has been extensively used in chemical biology research without reports of significant cytotoxicity at relevant concentrations.
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| References | |
| Additional Infomation |
AP1867-3-(Methoxyethylamine) is a research-grade chemical building block, not a clinical drug. It enables the synthesis of FKBP12 F36V-directed PROTAC degraders through its aminoethoxy linker handle, which can be conjugated to E3 ubiquitin ligase ligands such as VHL or CRBN binders. This approach allows selective protein degradation, complementing traditional inhibitor-based studies. As of the latest updates, this compound has not been approved for clinical use and is exclusively available for research purposes.
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| Molecular Formula |
C38H50N2O9
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|---|---|
| Molecular Weight |
678.811611652374
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| Exact Mass |
678.351
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| CAS # |
2127390-15-0
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| PubChem CID |
139600312
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| Appearance |
White to off-white solid powder
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| LogP |
5.8
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
18
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| Heavy Atom Count |
49
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| Complexity |
973
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| Defined Atom Stereocenter Count |
3
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| SMILES |
O([C@H](C1C=CC=C(C=1)OCCN)CCC1C=CC(=C(C=1)OC)OC)C([C@H]1CCCCN1C([C@@H](C1C=C(C(=C(C=1)OC)OC)OC)CC)=O)=O
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| InChi Key |
IUXMLUSGUQVKAO-RWSKJCERSA-N
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| InChi Code |
InChI=1S/C38H50N2O9/c1-7-29(27-23-34(45-4)36(47-6)35(24-27)46-5)37(41)40-19-9-8-13-30(40)38(42)49-31(26-11-10-12-28(22-26)48-20-18-39)16-14-25-15-17-32(43-2)33(21-25)44-3/h10-12,15,17,21-24,29-31H,7-9,13-14,16,18-20,39H2,1-6H3/t29-,30-,31+/m0/s1
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| Chemical Name |
[(1R)-1-[3-(2-aminoethoxy)phenyl]-3-(3,4-dimethoxyphenyl)propyl] (2S)-1-[(2S)-2-(3,4,5-trimethoxyphenyl)butanoyl]piperidine-2-carboxylate
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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) |
DMSO : ~240 mg/mL (~353.56 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 6 mg/mL (8.84 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.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 60.0 mg/mL clear DMSO 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 (8.84 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (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 60.0 mg/mL clear DMSO 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: ≥ 6 mg/mL (8.84 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.4732 mL | 7.3658 mL | 14.7317 mL | |
| 5 mM | 0.2946 mL | 1.4732 mL | 2.9463 mL | |
| 10 mM | 0.1473 mL | 0.7366 mL | 1.4732 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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