| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| Targets |
TED-347 targets the interaction between the transcriptional coactivator YAP (Yes-associated protein) and the TEAD (Transcriptional enhancer factor) family of transcription factors. This protein-protein interaction is a key downstream effector of the Hippo signaling pathway, which regulates organ size, tissue homeostasis, and tumorigenesis. By covalently and irreversibly binding to an allosteric site on TEAD4, TED-347 inhibits this interaction, thereby blocking TEAD-mediated transcription.
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| ln Vitro |
The motility of GBM43 sperm is inhibited by TED-347 (0.5-100 μM; 48 hours) [1]. The co-immunoprecipitation of Myc-tagged TEAD4 and FLAG-tagged Yap1 is inhibited by TED-347 (5 μM; 48 hours) [1]. The calibrator levels are significantly reduced in -347 (10 μM; 48 hours) CTGF [1]. Cells transfected with the TEAD reporter gene exhibit decreased reporter activity in response to TED-347 (0.5-100 μM; 24 hours). In GBM43 cells, TED-347 (0.5-100 μM) also suppresses TEAD4 transcriptional activity [1]. TED-347 exhibits the same level of efficacy as TEAD2 inhibition and is selective for TEADs. It has been observed that TED-347 (0.1-100 μM; 24-48 hours) mimicking TED-347 (1-100 μM) did not inhibit Cav2.2 αβ protein-protein reactions or uPAR uPA. The precision of TEAD4 Yap1 binding affinity is impacted by the non-covalent binding of TED-347 to TEAD4 [1]. TED-347 exhibits a response t1/2∞ of 18.2 hours and a maximal inactivation of 0.038 hours [1].
TED-347 exhibits potent in vitro activity. It inhibits the binding of CPM to N-terminal His6-tagged human TEAD4 with an IC50 of 800.0 nM and shows a Ki value of 10400.0 nM. It inhibits the TEAD4-Yap1 protein-protein interaction with an EC50 of 5.9 μM. It specifically and covalently binds to Cys-367 within the central pocket of TEAD4. |
| ln Vivo |
TED-347 has demonstrated in vivo antitumor activity. It blocks TEAD transcriptional activity, which is critical for the growth and survival of certain cancers. Its activity has been shown to reduce the viability of patient-derived glioblastoma cell lines. Further in vivo studies are needed to fully characterize its efficacy.
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| Enzyme Assay |
In vitro assays for TED-347 involve measuring its inhibition of the YAP-TEAD protein-protein interaction. These assays can be performed using surface plasmon resonance (SPR) or fluorescence polarization to measure the binding affinity. Cellular assays use a luciferase reporter under the control of TEAD-responsive elements to measure transcriptional activity. The compound's covalent binding can be assessed using mass spectrometry.
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| Cell Assay |
Cell viability assay [1]
Cell Types: GBM43 glioblastoma cell line Tested Concentrations: 0.5, 1, 10, 100 μM Incubation Duration: 48 hrs (hours) Experimental Results: Inhibited GBM43 cancer cell viability, inhibited GBM43 cell viability by 30% at 10 μM. Western Blot Analysis[1] Cell Types: HEK-293 Cell Tested Concentrations: 5 μM Incubation Duration: 48 hrs (hours) Experimental Results: Significant loss of Myc-tagged TEAD4 co-immunoprecipitated with FLAG-tagged Yap1. RT-PCR[1] Cell Types: HEK-293 Cell Tested Concentrations: 10 μM Incubation Duration: 48 hrs (hours) Experimental Results: CTGF transcript levels were Dramatically diminished compared to control cells and had negative effects on TEAD mutant transcriptional activity and protein-protein interactions Cell culture was not inhibited. In vitro cellular assays for TED-347 are conducted in cancer cell lines, such as glioblastoma cells. Cells are treated with the compound, and cell viability is measured using MTT or CellTiter-Glo assays. TEAD transcriptional activity is assessed using a luciferase reporter assay. The expression of YAP/TEAD target genes (e.g., CTGF, CYR61) is measured by qPCR. |
| Animal Protocol |
In vivo animal experiments with TED-347 are conducted in mouse xenograft models of cancer, likely glioblastoma. Tumor-bearing mice are administered TED-347, and tumor growth is monitored. Tumor tissues are harvested for analysis of TEAD transcriptional activity and target gene expression. Pharmacodynamic studies are performed to confirm target engagement and pathway inhibition.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for TED-347 are limited. It has a molecular weight of 313.70. The compound is soluble in DMSO and is typically stored as a powder at -20°C. Its half-life, bioavailability, and tissue distribution would need to be characterized in preclinical studies.
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| Toxicity/Toxicokinetics |
Toxicological data for TED-347 are not extensively published. The compound is intended for research use only and is not approved for human therapeutic use. Standard laboratory safety precautions should be followed when handling this compound.
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| References | |
| Additional Infomation |
TED-347 is a novel, covalent, irreversible, and allosteric YAP-TEAD protein-protein interaction inhibitor. It has antitumor activity and blocks TEAD transcriptional activity. It specifically binds to Cys-367 in TEAD4 and reduces the viability of glioblastoma cell lines.
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| Molecular Formula |
C15H11CLF3NO
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|---|---|
| Molecular Weight |
313.7022
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| Exact Mass |
313.048
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| CAS # |
2378626-29-8
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| Related CAS # |
2378626-29-8;
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| PubChem CID |
137796964
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| Appearance |
Light yellow to green yellow solid powder
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| LogP |
5.2
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
21
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| Complexity |
361
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC([H])([H])C(C1=C([H])C([H])=C([H])C([H])=C1N([H])C1=C([H])C([H])=C([H])C(C(F)(F)F)=C1[H])=O
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| InChi Key |
JPVDFGYNLUBCSD-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C15H11ClF3NO/c16-9-14(21)12-6-1-2-7-13(12)20-11-5-3-4-10(8-11)15(17,18)19/h1-8,20H,9H2
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| Chemical Name |
2-chloro-1-[2-[3-(trifluoromethyl)anilino]phenyl]ethanone
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| Synonyms |
TED347 TED 347
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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 (~318.78 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 6.25 mg/mL (19.92 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 62.5 mg/mL clear DMSO stock solution to 900 μL corn oil and mix evenly. Solubility in Formulation 2: 2.5 mg/mL (7.97 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.1878 mL | 15.9388 mL | 31.8776 mL | |
| 5 mM | 0.6376 mL | 3.1878 mL | 6.3755 mL | |
| 10 mM | 0.3188 mL | 1.5939 mL | 3.1878 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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