TED-347 (TED347) is a novel, covalent/irreversible, and allosteric YAP-TEAD protein-protein interaction inhibitor with anticancer activity. It inhibits TEAD4-Yap1 protein-protein interaction with an EC50 of 5.9 μM. It acts by covalently binding to Cys-367 within the central pocket of TEAD4 with a Ki of 10.3 μM, thus blocking TEAD transcriptional activity.

Physicochemical Properties

Molecular Formula	C15H11CLF3NO
Molecular Weight	313.7022
Exact Mass	313.048
CAS #	2378626-29-8
Related CAS #	2378626-29-8;
PubChem CID	137796964
Appearance	Light yellow to green yellow solid powder
LogP	5.2
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	4
Heavy Atom Count	21
Complexity	361
Defined Atom Stereocenter Count	0
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
InChi Key	JPVDFGYNLUBCSD-UHFFFAOYSA-N
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
Chemical Name	2-chloro-1-[2-[3-(trifluoromethyl)anilino]phenyl]ethanone
Synonyms	TED347 TED 347
HS Tariff Code	2934.99.9001
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)

Biological Activity

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].
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.
References	[1]. Small-Molecule Covalent Modification of Conserved Cysteine Leads to Allosteric Inhibition of the TEAD⋅Yap Protein-Protein Interaction. Cell Chem Biol. 2019 Mar 21;26(3):378-389.e13.

Solubility Data

Solubility (In Vitro)

DMSO : ~100 mg/mL (~318.78 mM)

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.