| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
YAP/TAZ inhibitor-3 targets the protein-protein interaction between TEAD transcription factors (TEAD1-4) and the transcriptional coactivators YAP and TAZ. This interaction is essential for the transcriptional activity of YAP/TAZ, which regulate genes involved in cell proliferation, survival, and migration. The compound inhibits TEAD1-4 palmitoylation, a post-translational modification that is critical for the TEAD-YAP/TAZ interaction. By disrupting this interaction, the compound prevents YAP/TAZ from activating their downstream target genes, thereby inhibiting the oncogenic functions of the Hippo pathway.
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| ln Vitro |
YAP/TAZ inhibitor-3 shows potent in vitro activity with firefly luciferase inhibitory activity exhibiting an IC50 of less than 0.1 μM. The compound inhibits the proliferation of a variety of mesothelioma cells, including those with homozygous NF2 mutations, with GI50 values ranging from 8 to 74 nM. In HEK293T cells expressing TEAD1-4, the compound inhibits TEAD palmitoylation when used at a concentration of 3 μM. The potent activity against NF2-mutant mesothelioma cells highlights its potential for treating tumors that are dependent on YAP/TAZ signaling.
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| ln Vivo |
In vivo activity of YAP/TAZ inhibitor-3 has been demonstrated in preclinical cancer models, particularly for mesothelioma and other tumors with dysregulated Hippo signaling. The compound's ability to inhibit TEAD-YAP/TAZ interaction translates to suppression of tumor growth in xenograft models. The compound is suitable for in vivo formulation, with solubility in 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% Saline at 3.3 mg/mL (8.48 mM). This formulation enables administration via intraperitoneal or oral routes for evaluating antitumor efficacy in animal models.
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| Enzyme Assay |
Non-cell-based binding assays for YAP/TAZ inhibitor-3 typically involve biochemical methods to measure the inhibition of TEAD-YAP/TAZ protein-protein interaction. A standard protocol includes using fluorescence polarization (FP) or AlphaScreen technology with purified TEAD and YAP/TAZ proteins. The compound is incubated with the protein components at various concentrations (typically 0.001–100 μM) in assay buffer, and the displacement of a fluorescently labeled peptide or the reduction of signal is measured to determine the IC50. Surface plasmon resonance (SPR) may also be employed to directly measure binding affinity to TEAD proteins.
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| Cell Assay |
Cellular assays for YAP/TAZ inhibitor-3 typically utilize mesothelioma cell lines, particularly those with NF2 mutations that are dependent on YAP/TAZ signaling. A representative protocol involves culturing cells (e.g., NCI-H226 or MSTO-211H) in appropriate medium, treating with YAP/TAZ inhibitor-3 at various concentrations (0.001–100 μM) for 48–72 hours, and assessing cell viability using CellTiter-Glo or MTT assays. To confirm on-target activity, YAP/TAZ target gene expression (e.g., CTGF, CYR61, ANKRD1) is measured by qRT-PCR, and TEAD transcriptional activity is assessed using a firefly luciferase reporter assay.
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| Animal Protocol |
In vivo animal studies with YAP/TAZ inhibitor-3 are conducted in xenograft mouse models of mesothelioma or other YAP/TAZ-dependent tumors. A typical protocol involves subcutaneous implantation of tumor cells (e.g., NCI-H226 or MSTO-211H) in immunodeficient mice, allowing tumors to reach approximately 100–200 mm³. YAP/TAZ inhibitor-3 is administered via oral gavage or intraperitoneal injection at doses determined from pharmacokinetic studies (typically 10–100 mg/kg, once or twice daily). Tumor growth and body weight are monitored, and tumors are harvested for histopathological analysis and pharmacodynamic assessment of YAP/TAZ target gene expression.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of YAP/TAZ inhibitor-3 have been characterized for in vivo applications. The compound has a molecular weight of 389.37 g/mol and moderate lipophilicity, suggesting reasonable oral bioavailability. The compound is soluble in DMSO at ≥80 mg/mL and has been formulated for in vivo administration using a vehicle of 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% Saline (3.3 mg/mL, 8.48 mM). Standard PK parameters including half-life, clearance, and volume of distribution can be determined from plasma concentration-time profiles following single and multiple dose administration.
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| Toxicity/Toxicokinetics |
As a research compound, YAP/TAZ inhibitor-3 is not intended for human therapeutic use, and comprehensive toxicological data are limited to preclinical studies. Standard safety assessments would include cytotoxicity screening in normal cell lines, hERG channel inhibition testing to evaluate cardiac safety, and preliminary toxicology studies in animal models to determine maximum tolerated dose and identify potential target organs of toxicity. The compound is stored as a powder at -20°C for up to 3 years and in solvent at -80°C for 1 year.
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| References | |
| Additional Infomation |
YAP/TAZ inhibitor-3 (Compound 24, also known as VT3989) is a valuable research tool for studying the Hippo signaling pathway and its role in cancer. The compound is referenced in the primary literature for its potent inhibition of TEAD-YAP/TAZ interaction and its antiproliferative activity against mesothelioma cells. The Hippo pathway is a key regulator of organ size and tissue homeostasis, and its dysregulation is implicated in various cancers, making YAP/TAZ inhibitors attractive targets for drug development. YAP/TAZ inhibitor-3 is suitable for both in vitro and in vivo studies, providing researchers with a tool to investigate the therapeutic potential of targeting the Hippo pathway.
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| Exact Mass |
389.124
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| CAS # |
2506273-81-8
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| PubChem CID |
155214091
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
28
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| Complexity |
520
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C[C@H](CO)NC(=O)C1=CC2=C(C=C1)C(=CC=C2)OC3=CC=C(C=C3)C(F)(F)F
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| InChi Key |
FJIVCOAHSKDOAC-CYBMUJFWSA-N
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| InChi Code |
InChI=1S/C21H18F3NO3/c1-13(12-26)25-20(27)15-5-10-18-14(11-15)3-2-4-19(18)28-17-8-6-16(7-9-17)21(22,23)24/h2-11,13,26H,12H2,1H3,(H,25,27)/t13-/m1/s1
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| Chemical Name |
N-[(2R)-1-hydroxypropan-2-yl]-5-[4-(trifluoromethyl)phenoxy]naphthalene-2-carboxamide
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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 :≥ 125 mg/mL (~321.03 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
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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