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Description: Degrades mutant FKBP12F36V fusion proteins; useful alternative to genetic methods for target validation
Chemical Name: 1-[(2S)-1-Oxo-2-(3,4,5-trimethoxyphenyl)butyl]-(2S)-2-piperidinecarboxylate (1R)-3-(3,4-dimethoxyphenyl)-1-[2-[2-[[6-[[2-(2,6-dioxo-3-piperidinyl)-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]oxy]hexyl]amino]-2-oxoethoxy]phenyl]propyl ester
Purity: ≥98% (HPLC)
Biological Activity
Degrader targeting mutant FKBP12F36V fusion proteins. Comprises a ligand selective for F36V single-point mutated FKBP12, a linker and a cereblon-binding ligand. FKBP12F36V can be expressed as a fusion with a target protein of interest using genome engineering techniques (via transgene expression or CRISPR-mediated locus-specific knock-in). Application of dTAG-13 induces rapid, reversible and selective degradation of FKBP12F36V fusion proteins in vitro and in vivo. dTAG is generalizable to a range of fusion proteins; useful as an alternative to genetic methods for target validation.
Plasmid vectors for the lentiviral expression and CRISPR-mediated knock-in of FKBP12F36V are available from Addgene.
Licensing Information
Sold under license from Dana-Farber Cancer Institute
Technical Data
| M. Wt | 1049.18 |
| Formula | C57H68N4O15 |
| Storage | Store at -20°C |
| Purity | ≥98% (HPLC) |
| CAS Number | 2064175-41-1 |
| PubChem ID | 124187630 |
| InChI Key | BJFBRLAWLPZOMJ-QHVFGHLPSA-N |
| Smiles | CC[C@@H](C1=CC(OC)=C(C(OC)=C1)OC)C(N2CCCC[C@H]2C(O[C@@H](C3=C(C=CC=C3)OCC(NCCCCCCOC4=C5C(N(C(C5=CC=C4)=O)C6CCC(NC6=O)=O)=O)=O)CCC7=CC(OC)=C(C=C7)OC)=O)=O |
The technical data provided above is for guidance only. For batch specific data refer to the Certificate of Analysis.
Tocris products are intended for laboratory research use only, unless stated otherwise.
Solubility Data
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 52.46 | 50 | |
| ethanol | 20.98 | 20 |
Preparing Stock Solutions
The following data is based on the product molecular weight 1049.18. Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 0.5 mM | 1.91 mL | 9.53 mL | 19.06 mL |
| 2.5 mM | 0.38 mL | 1.91 mL | 3.81 mL |
| 5 mM | 0.19 mL | 0.95 mL | 1.91 mL |
| 25 mM | 0.04 mL | 0.19 mL | 0.38 mL |
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References
References are publications that support the biological activity of the product.
Erb et al (2017) Transcription control by the ENL YEATS domain in acute leukaemia. Nature 543 270 PMID: 28241139
Nabet et al (2018) The dTAG system for immediate and target-specific protein degradation. Nat.Chem.Biol. 14 431 PMID: 29581585
Bensimon et al (2020) Targeted degradation of SLC transporters reveals amenability of multi-pass transmembrane proteins to ligand-induced proteolysis. Cell Chem.Biol. 27 728 PMID: 32386596
If you know of a relevant reference for dTAG-13, please let us know.
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Keywords: dTAG-13, dTAG-13 supplier, dTAG13, degraders, degrades, degradation, FKBP12F36V, fusion, protein, mutant, PROTAC, proteolysis, targeting, chimera, cereblon, TAG, Degradation, Platform, 6605, Tocris Bioscience
Citations for dTAG-13
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Reviews for dTAG-13
Average Rating: 5 (Based on 3 Reviews.)
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dTAG-13 treatment of FKBP tagged over expressed protein in glioma cell lines.
By
Anonymous on 07/02/2020
Assay Type: In Vitro
Species: Human
Cell Line/Tissue: Glioma
Assayed the degradation of FKBP-tagged-protein with HA tag in glioma cells using dTAG-13 at 500nM concentration for 0h, 4h, 6h and 24h time intervals. Untransfected cells has no HA signal and in transfected cells with dTAG-13 treatment lead to complete degradation of FKBP-tagged-protein in whole cell lysates
Knockdown of FKBP-tagged Chromatin Protein.
By
Sam Weeks on 01/30/2020
Assay Type: In Vitro
Species: Mouse
Cell Line/Tissue: mESC
Assayed different dTag concentrations (50nm, 250nm, 500nm) for the knockdown of a FKBP-tagged chromatin-bound protein (180kDa). Whole cell lysate (RIPA) revealed no change to WT cells (150kDa) and considerable knockdown in all conditions after just an hour of treatment.
Works better than expected.
By
Abderhman Abuhashem on 10/14/2019
Assay Type: In Vitro
Species: Mouse
Cell Line/Tissue: E14 (mouse Embryonic Stem cells)
Used dTAG-13 to degrade a transgene tagged with FKBM12-F36V and HA tags to visualize the protein.
This is a western blot probed for HA tag to track degradation. All samples are treated with 500nM dTAG-13. Lanes are: 1) parental cell line, 2) control (no treatment), 3) 30 mins of treatment, 4) 1hr of treatment, 5) 2hrs of treatment, 6) 4hrs of treatment, 7) 6hrs of treatment. The constructs, as shown by the western, was degraded almost entirely (>98% quantified), within 30 mins. I have tested batch 2 of this product at conc. as low as 50nM and still just as effective. No apparent toxicity to cells. Extremely satisfied.
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Targeted Protein Degradation Research Product Guide
This brochure highlights the tools and services available from Bio-Techne to support Targeted Protein Degradation research, including:
- Active Degraders
- Degrader Building Blocks
- Custom Degrader Services
- UPS Proteins and Assays
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Targeted Protein Degradation Poster
Degraders (e.g. PROTACs) are bifunctional small molecules, that harness the Ubiquitin Proteasome System (UPS) to selectively degrade target proteins within cells. They consist of three covalently linked components: an E3 ubiquitin ligase ligand, a linker and a ligand for the target protein of interest. Authored in-house, this poster outlines the generation of a toolbox of building blocks for the development of Degraders. The characteristics and selection of each of these components are discussed. Presented at EFMC 2018, Ljubljana, Slovenia