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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 for dTAG-13
dTAG-13 is a degrader targeting mutant FKBP12F36V fusion proteins. Comprises a ligand selective for F36V single-point mutated FKBP12, a linker and a cereblon-binding ligand. 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.
Negative control (Cat. No. 6916) also available.
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.
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 for dTAG-13
| 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 for dTAG-13
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 52.46 | 50 | |
| ethanol | 20.98 | 20 |
Preparing Stock Solutions for dTAG-13
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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Product Datasheets for dTAG-13
References for dTAG-13
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
Abuhashem et al (2022) Generation of knock-in degron tags for endogenous proteins in mice using the dTAG system. STAR Protoc. 3 101660 PMID: 36097386
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, PROTACs, in, vivo, TAG, Degradation, Platform, 6605, Tocris Bioscience
21 Citations for dTAG-13
Citations are publications that use Tocris products. Selected citations for dTAG-13 include:
Kaji et al (2020) Characterization of cereblon-dependent targeted protein degrader by visualizing the spatiotemporal ternary complex formation in cells Sci.Rep. 10 3088 PMID: 32080280
Sahillioglu et al (2021) CRASH-IT switch enables reversible and dose-dependent control of TCR and CAR T-cell function. Cancer Immunol.Res. 9 999 PMID: 34193461
Kristian et al (2021) Generation of locus-specific degradable tag knock-ins in mouse and human cell lines. STAR Protoc 2 100575 PMID: 34151298
Hao et al (2021) Dipeptidyl peptidase 9 sets a threshold for CARD8 inflammasome formation by sequestering its active C-terminal fragment. Immunity 54 1392-1404.e10 PMID: 34019797
William P et al (2021) Gene-specific quantification of nascent transcription following targeted degradation of endogenous proteins in cultured cells. STAR Protoc 2 101000 PMID: 34917979
Abuhashem et al (2022) Generation of knock-in degron tags for endogenous proteins in mice using the dTAG system. STAR Protoc. 3 101660 PMID: 36097386
Xavier et al (2019) An efficient auxin-inducible degron system with low basal degradation in human cells. Nat Methods 16 866-869 PMID: 31451765
Rutger A F et al (2023) CasTuner is a degron and CRISPR/Cas-based toolkit for analog tuning of endogenous gene expression. Nat Commun 14 3225 PMID: 37270532
Cristian et al (2023) MYC regulates CSF-1 expression via microRNA 17/20a to modulate tumor-associated macrophages in osteosarcoma. JCI Insight PMID: 37279073
Yuan et al (2022) Effective Menin inhibitor-based combinations against AML with MLL rearrangement or NPM1 mutation (NPM1c). Blood Cancer J 12 5 PMID: 35017466
Daniel A et al (2022) A ubiquitin-independent proteasome pathway controls activation of the CARD8 inflammasome. J Biol Chem 298 102032 PMID: 35580636
Francisca et al (2022) Systematic profiling of conditional degron tag technologies for target validation studies. Nat Commun 13 5495 PMID: 36127368
Rafael et al (2022) BRD2 compartmentalizes the accessible genome. Nat Genet 54 481-491 PMID: 35410381
Fei et al (2022) Regulation of cohesin-mediated chromosome folding by PDS5 in mammals. EMBO Rep 23 e54853 PMID: 36129789
Xin et al (2022) A TET1-PSPC1-Neat1 molecular axis modulates PRC2 functions in controlling stem cell bivalency. Cell Rep 39 110928 PMID: 35675764
Anja et al (2022) NASP maintains histone H3-H4 homeostasis through two distinct H3 binding modes. Nucleic Acids Res 50 5349-5368 PMID: 35489058
Neil et al (2022) Xist-mediated silencing requires additive functions of SPEN and Polycomb together with differentiation-dependent recruitment of SmcHD1. Cell Rep 39 110830 PMID: 35584662
Anna-Katerina et al (2022) Generation of knock-in degron tags for endogenous proteins in mice using the dTAG system. STAR Protoc 3 101660 PMID: 36097386
Tibor et al (2022) The histone methyltransferase SETD2 negatively regulates cell size. J Cell Sci 135 PMID: 36052643
Ma et al (2023) Engineered PROTAC-CID systems for mammalian inducible gene regulation. J Am Chem Soc 145 1593 PMID: 36626587
Orth-He et al (2023) Protein folding stress potentiates NLRP1 and CARD8 inflammasome activation. Cell Rep 42 111965 PMID: 36649711
Do you know of a great paper that uses dTAG-13 from Tocris? Please let us know.
Reviews for dTAG-13
Average Rating: 5 (Based on 4 Reviews.)
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Degradation of Myc fusion protein.
By
Bikesh Nirala on 06/21/2022
Assay Type: In Vitro
Species: Mouse
Cell Line/Tissue: Murine cell lines
I tested this product to degrade FFKBP12-Myc protein. It is working nicely.
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.
Literature in this Area
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TPD and Induced Proximity Research Product GuideUpdated
This brochure highlights the tools and services available from Bio-Techne to support your Targeted Protein Degradation and Induced Proximity research, including:
- Active Degraders
- TAG Degradation Platform
- Degrader Building Blocks
- Assays for Protein Degradation
- Induced Proximity Tools
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
