| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| Other Sizes |
| Targets |
FKBP12F36V - selective binder (ligand); no IC50/Ki/EC50 values for AP1867 alone are reported in this study. AP1867 was used as the FKBP12F36V-directed ligand component in dTAG molecules (dTAG-7, dTAG-13, dTAG-48, dTAG-51). [1]
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|---|---|
| ln Vitro |
Wild-type FKBP (Kd=67 nM) is bound by AP1867 [2].
AP1867 itself was not directly tested for in vitro activity in this study. The dTAG molecules incorporating AP1867 as the FKBP12F36V-binding moiety demonstrated selective degradation of FKBP12F36V fusion proteins. No direct in vitro activity data for AP1867 alone was reported. [1] |
| Enzyme Assay |
No enzyme assay for AP1867 alone was performed. However, AP1867 was used as the FKBP12F36V-directed ligand in the design of dTAG molecules. Biochemical AlphaScreen assays with dTAG molecules demonstrated engagement with FKBP12F36V, where the AP1867 moiety mediates binding to FKBP12F36V. In the CRBN-DDB1/FKBP12F36V dimerization assay, dTAG molecules containing the AP1867 moiety induced complex formation between CRBN-DDB1 and FKBP12F36V. [1]
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| Cell Assay |
No cell-based assay for AP1867 alone was performed. AP1867 is described as a synthetic ligand that selectively binds FKBP12F36V over FKBP12WT. In cellular degradation assays using FKBP12WT-Nluc or FKBP12F36V-Nluc reporter systems, dTAG molecules containing the AP1867 moiety showed selective degradation of FKBP12F36V-Nluc with limited effect on FKBP12WT-Nluc, consistent with the selectivity of AP1867 for FKBP12F36V. [1]
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| References | |
| Additional Infomation |
AP1867 is a "bumped" synthetic ligand that creates a cavity in FKBP12F36V allowing selective recognition and binding. This ligand was previously described by Ariad Pharmaceuticals as part of a chemical dimerizer system. The engineered FKBP12F36V mutant contains a F36V substitution that creates a pocket enabling selective binding of AP1867 while preventing binding of the natural ligand FK506. In the dTAG system, AP1867 is appended to CRBN ligands (thalidomide derivatives) via linkers to create heterobifunctional degraders (dTAG-7, dTAG-13, dTAG-48, dTAG-51). The AP1867 moiety engages FKBP12F36V fusion proteins while the CRBN ligand recruits the E3 ubiquitin ligase complex, leading to ubiquitination and proteasomal degradation of the target protein. This approach allows selective degradation of FKBP12F36V-tagged proteins of interest without affecting endogenous FKBP12WT. [1]
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| Molecular Formula |
C38H47NO11
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|---|---|
| Molecular Weight |
693.7799
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| Exact Mass |
693.314
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| CAS # |
195514-23-9
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| PubChem CID |
444590
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
6.3
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
18
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| Heavy Atom Count |
50
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| Complexity |
1050
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| Defined Atom Stereocenter Count |
3
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| SMILES |
O([C@@]([H])(C1C([H])=C([H])C([H])=C(C=1[H])OC([H])([H])C(=O)O[H])C([H])([H])C([H])([H])C1C([H])=C([H])C(=C(C=1[H])OC([H])([H])[H])OC([H])([H])[H])C([C@]1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])N1C([C@]([H])(C1C([H])=C(C(=C(C=1[H])OC([H])([H])[H])OC([H])([H])[H])OC([H])([H])[H])C([H])([H])C([H])([H])[H])=O)=O
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| InChi Key |
XCCRAOPQCACRFC-OIFRRMEBSA-N
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| InChi Code |
InChI=1S/C38H47NO11/c1-7-28(26-21-33(46-4)36(48-6)34(22-26)47-5)37(42)39-18-9-8-13-29(39)38(43)50-30(25-11-10-12-27(20-25)49-23-35(40)41)16-14-24-15-17-31(44-2)32(19-24)45-3/h10-12,15,17,19-22,28-30H,7-9,13-14,16,18,23H2,1-6H3,(H,40,41)/t28-,29-,30+/m0/s1
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| Chemical Name |
2-[3-[(1R)-3-(3,4-dimethoxyphenyl)-1-[(2S)-1-[(2S)-2-(3,4,5-trimethoxyphenyl)butanoyl]piperidine-2-carbonyl]oxypropyl]phenoxy]acetic acid
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| Synonyms |
dTAG acid AP 1867 AP1867AP-1867
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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) |
DMSO : ~100 mg/mL (~144.14 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.00 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 20.8 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: ≥ 2.08 mg/mL (3.00 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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.4414 mL | 7.2069 mL | 14.4138 mL | |
| 5 mM | 0.2883 mL | 1.4414 mL | 2.8828 mL | |
| 10 mM | 0.1441 mL | 0.7207 mL | 1.4414 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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