dTAG-Fluorescein
dTAG-Fluorescein is a fluorescent acceptor probe and heterobifunctional proteolysis targeting chimeric molecule (PROTAC).dTAG-Fluorescein functions in Homogeneous Time Resolved Fluorescence (HTRF) competitive displacement binding assays to measure binding affinity to His-FKBP12(F36V).dTAG-Fluorescein recruits von Hippel-Lindau or CRBN E3 ligase complexes to drive selective degradation of FKBP12F36V-tagged proteins, with limited activity towards FKBP12WT and IKZF1.
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- CAS No.: 2365116-48-7
- Formule: C59H60N2O15
- Masse moléculaire:1037.11
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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FKBP12 |
dTAG-Fluorescein (dTAG-13) (30 minutes; 1 hour) potently engages purified CRBN-DDB1 protein in a ligand-displacement AlphaScreen assay[5].
dTAG-Fluorescein (dTAG-13) effectively induces heterodimerization of purified CRBN-DDB1 and FKBP12F36V proteins in a dimerization AlphaScreen assay[5].
dTAG-Fluorescein (dTAG-13) (100 nM; 1-24 h) potently and selectively induces CRBN-dependent degradation of FKBP12F36V-Nluc fusion protein in 293FTWT cells, with activity detectable at 100 nM within 1 hour of treatment[5].
dTAG-Fluorescein (dTAG-13) (1 h) rapidly induces degradation of BRD4(short)-FKBP12F36V fusion protein in MV4;11 cells without affecting endogenous FKBP12WT[5].
dTAG-Fluorescein (dTAG-13) selectively induces degradation of endogenously tagged BRD4-FKBP12F36V fusion protein in 293T knock-in cells without affecting BRD2, BRD3, or endogenous FKBP12WT[5].
dTAG-Fluorescein (dTAG-13) (50 nM; 1-8 h) potently induces degradation of diverse nuclear and cytoplasmic FKBP12F36V fusion proteins (including KRASG12V, EZH2, HDAC1, MYC, and PLK1) in MV4;11 cells, with activity detectable at 50 nM and varying degradation kinetics across targets[5].
dTAG-Fluorescein (dTAG-13) (1-4 h) selectively depletes FKBP12F36V-KRASG12V fusion protein in NIH/3T3 cells, achieving 58.3% depletion within 1 hour and 88.6% depletion within 4 hours, as measured by quantitative proteomics[5].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MV4;11 cells stably expressing FKBP12F36V-KRASG12V, FKBP12F36V-EZH2, HDAC1-FKBP12F36V, MYC-FKBP12F36V, or PLK1-FKBP12F36V fusion proteins
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Concentration:50 nM
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Incubation Time:1 h, 4 h, 8 h
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Result:Potently degraded each fusion chimera with as little as 50 nM dTAG-13.
Caused pronounced degradation of HDAC1-FKBP12F36V, MYC-FKBP12F36V, FKBP12F36V-EZH2, and PLK1-FKBP12F36V within 1 hour.
Achieved near-complete degradation of FKBP12F36V-KRASG12V after 4 to 8 hours.
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Cell Line:NIH/3T3 cells stably expressing FKBP12F36V-KRASG12V fusion protein
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Concentration:1 µM
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Incubation Time:1 h, 24 h, 48 h, 72 h; unspecified time (inhibitor pre-treatment)
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Result:Led to rapid and pronounced degradation of FKBP12F36V-KRASG12V, with a corresponding decrease in phospho-MEK and phospho-AKT to baseline levels within 1 hour.
Prevented fusion protein degradation when cells were pre-treated with carfilzomib, MLN4924, or lenalidomide.
Led to rapid recovery of FKBP12F36V-KRASG12V and phospho-MEK, phospho-ERK, and phospho-AKT levels within 1 hour after washout.
Chemical Information
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CAS No. 2365116-48-7
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Masse moléculaire 1037.11
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Formule C59H60N2O15
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SMILES
O=C1OC2(C3=CC=C(O)C=C3OC4=CC(O)=CC=C42)C5=CC(C(NCCOC6=CC([C@@H](CCC7=CC(OC)=C(C=C7)OC)OC([C@H]8N(CCCC8)C([C@H](C9=CC(OC)=C(C(OC)=C9)OC)CC)=O)=O)=CC=C6)=O)=CC=C51
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
[1]. Islam S, et al. A Tandem-Affinity Purification Method for Identification of Primary Intracellular Drug-Binding Proteins. ACS Chem Biol. 2024;19(2):233-242. [Content Brief]
[3]. Nabet B, et al. Rapid and direct control of target protein levels with VHL-recruiting dTAG molecules. Nat Commun. 2020;11(1):4687. Published 2020 Sep 18. [Content Brief]
[4]. Yenerall P, et al. Use of the dTAG system in vivo to degrade CDK2 and CDK5 in adult mice and explore potential safety liabilities. Toxicol Sci. 2023;194(1):53-69. [Content Brief]
[5]. Nabet B, et al. The dTAG system for immediate and target-specific protein degradation. Nat Chem Biol. 2018;14(5):431-441. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)