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| Targets |
FKBP12 PROTAC dTAG-13 targets FKBP12F36V, a mutant form of FKBP12 that can be fused in-frame to a protein of interest. The compound also engages CRBN, an E3 ubiquitin ligase, which mediates the ubiquitination and subsequent proteasomal degradation of the target protein. By linking FKBP12F36V to CRBN, dTAG-13 induces selective degradation of FKBP12F36V fusion proteins without affecting wild-type FKBP12. This system enables inducible protein degradation for functional studies.
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| ln Vitro |
FKBP12F36V-Nluc levels in 293FTWT cells were successfully decreased by TAG-13 (1-1000 nM; 4 hours; 293FTWT cells) treatment, suggesting that CRBN is necessary for the observed results [1]. When dTAG-13 was applied to MV4;11 cells that expressed BRD4(short)-FKBP12F36V, BRD4 was severely degraded. BRD4 rapidly degraded after receiving dTAG-13 treatment in less than an hour. In heterozygous and homozygous knock-in clones, dTAG-13 treatment causes BRD4 fusion chimeras to degrade quickly and effectively, but it has no effect on endogenous FKBP12WT [1].
In vitro, FKBP12 PROTAC dTAG-13 is a small molecule PROTAC that selectively degrades FKBP12F36V fusion proteins without affecting wild-type FKBP12. In cell lines such as 293T, PATU-8988T, and EOL-1, treatment with dTAG-13 (500 nM for 4 hours) effectively degrades FKBP12F36V fusion targets like FKBP12F36V-KRASG12V or FKBP12F36V-ABL1 and inhibits downstream signaling. The degradation activity is dose-dependent within the concentration range of 10-500 nM. This makes dTAG-13 a powerful tool for studying protein function and validating drug targets. |
| ln Vivo |
After transplantation of luc-FKBP12F36V-expressing MV4;11 cells into mouse bone marrow, the bioluminescence signal after vector or dTAG-13 administration was evaluated. A strong, quick, and long-lasting influence on the bioluminescence signal was seen four hours after dTAG-13 injection, demonstrating effective degradation of luc-FKBP12F36V. Twenty-eight hours following final treatment, cell bioluminescence was shown to rebound to levels comparable to vehicle and dTAG-13 treated groups [1].
In vivo, FKBP12 PROTAC dTAG-13 has demonstrated efficacy in a NOD/SCID mouse model bearing PATU-8988T FKBP12F36V-KRASG12V xenograft tumors. A single intraperitoneal (i.p.) dose of 35 mg/kg significantly reduced fusion protein expression in tumor tissues within 2 hours, with effects lasting for at least 12 hours. This rapid and sustained degradation demonstrates the compound's potential for in vivo target validation and pharmacodynamic studies. The in vivo activity of dTAG-13 supports its use in studying protein function in physiological contexts. |
| Enzyme Assay |
The cell-free assay for FKBP12 PROTAC dTAG-13 involves evaluating the binding affinity of the compound to FKBP12F36V and CRBN proteins. Binding assays are typically performed using surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC) to determine binding kinetics and thermodynamics. The compound's ability to induce ternary complex formation between FKBP12F36V and CRBN can be assessed using biochemical assays such as AlphaScreen or FRET. These assays quantify the efficiency of the PROTAC in bringing the target protein and E3 ligase into proximity.
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| Cell Assay |
Western blot analysis[1]
Cell Types: 293FTWT cells Tested Concentrations: 1 nM, 10 nM, 100 nM, 1000 nM Incubation Duration: 4 hrs (hours) Experimental Results: FKBP12F36V-Nluc levels were Dramatically diminished in 293FTWT cells. For in vitro cellular assays, FKBP12 PROTAC dTAG-13 is typically dissolved in DMSO and diluted in cell culture medium. Cells expressing FKBP12F36V fusion proteins are treated with dTAG-13 at concentrations ranging from 10-500 nM for 4-24 hours. Degradation of target proteins is assessed by western blotting using antibodies against the fusion protein or FKBP12. Downstream signaling inhibition is evaluated by phospho-specific antibodies. Dose-response and time-course experiments are performed to determine optimal degradation conditions. |
| Animal Protocol |
In vivo animal studies for FKBP12 PROTAC dTAG-13 are conducted in immunodeficient mice bearing xenograft tumors expressing FKBP12F36V fusion proteins. The compound is administered intraperitoneally (i.p.) at doses of 35 mg/kg. Tumor tissues are collected at various time points after dosing (2, 4, 8, 12, 24 hours). Degradation of the fusion protein is assessed by western blotting and immunohistochemistry. Pharmacodynamic studies evaluate the duration and extent of target degradation in vivo.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of FKBP12 PROTAC dTAG-13 include a molecular weight of 1049.17 g/mol and molecular formula C57H68N4O15. The compound has a predicted density of 1.260 g/cm3. It is stable as a powder at -20°C for up to 3 years and in solvent at -80°C for 1 year. The compound is typically formulated for in vivo administration using appropriate vehicles such as DMSO, PEG300, and saline. Specific PK parameters are available from published studies using this compound.
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| Toxicity/Toxicokinetics |
The toxicity profile of FKBP12 PROTAC dTAG-13 has been evaluated in preclinical studies. In mouse xenograft models, single i.p. doses of 35 mg/kg were well-tolerated. Standard toxicology studies would include assessment of body weight changes, organ histopathology, and clinical chemistry parameters. As with all PROTACs, potential off-target degradation and immunogenicity risks should be considered. The compound is intended for research use only and not for therapeutic applications in humans.
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| References | |
| Additional Infomation |
FKBP12 PROTAC dTAG-13 is a PROTAC-based heterobifunctional degrader, namely fKBP12 PROTAC dTAG-13 (dTAG-13). It selectively degrades FKBP12F36V, and FKBP12F36V is expressed co-framed with the target protein. FKBP12 PROTAC dTAG-13 effectively binds to both FKBP12F36V and CRBN, thereby selectively degrading FKBP12F36V.
FKBP12 PROTAC dTAG-13 is a heterobifunctional degrader that engages FKBP12F36V and CRBN to selectively degrade FKBP12F36V fusion proteins in a CRBN-dependent manner. It is used for target validation in drug discovery and to study protein function. In vitro, dTAG-13 (500 nM, 4 hours) effectively degrades FKBP12F36V fusion targets and inhibits downstream signaling in a dose-dependent manner (10-500 nM). In vivo, a single i.p. dose of 35 mg/kg reduces fusion protein expression in xenograft tumors within 2 hours, lasting at least 12 hours. dTAG-13 has not entered clinical trials and is strictly for research purposes. |
| Molecular Formula |
C₅₇H₆₈N₄O₁₅
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|---|---|
| Molecular Weight |
1049.16763687134
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| Exact Mass |
1048.468
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| CAS # |
2064175-41-1
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| Related CAS # |
2064175-41-1;
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| PubChem CID |
124187630
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| Appearance |
White to light yellow solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
1134.0±65.0 °C at 760 mmHg
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| Flash Point |
639.6±34.3 °C
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| Vapour Pressure |
0.0±0.3 mmHg at 25°C
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| Index of Refraction |
1.581
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| LogP |
6.98
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
15
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| Rotatable Bond Count |
27
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| Heavy Atom Count |
76
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| Complexity |
1930
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| Defined Atom Stereocenter Count |
3
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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=C4OCC(=O)NCCCCCCOC5=CC=CC6=C5C(=O)N(C6=O)C7CCC(=O)NC7=O
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| InChi Key |
BJFBRLAWLPZOMJ-VOSOTEEESA-N
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| InChi Code |
InChI=1S/C57H68N4O15/c1-7-37(36-32-47(71-4)52(73-6)48(33-36)72-5)54(65)60-29-14-12-19-41(60)57(68)76-43(25-22-35-23-26-44(69-2)46(31-35)70-3)38-17-10-11-20-42(38)75-34-50(63)58-28-13-8-9-15-30-74-45-21-16-18-39-51(45)56(67)61(55(39)66)40-24-27-49(62)59-53(40)64/h10-11,16-18,20-21,23,26,31-33,37,40-41,43H,7-9,12-15,19,22,24-25,27-30,34H2,1-6H3,(H,58,63)(H,59,62,64)/t37?,40?,41-,43+/m0/s1
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| Chemical Name |
(1R)-3-(3,4-dimethoxyphenyl)-1-(2-(2-((6-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)hexyl)amino)-2-oxoethoxy)phenyl)propyl
(2S)-1-(2-(3,4,5-trimethoxyphenyl)butanoyl)piperidine-2-carboxylate
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| Synonyms |
FKBP12 PROTAC dTAG-13 dTAG-13 dTAG13 dTAG 13
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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 : ~180 mg/mL (~171.56 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.9531 mL | 4.7657 mL | 9.5313 mL | |
| 5 mM | 0.1906 mL | 0.9531 mL | 1.9063 mL | |
| 10 mM | 0.0953 mL | 0.4766 mL | 0.9531 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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