| Size | Price | Stock | Qty |
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| 10mg |
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| Targets |
TEAD[1].
GNE-7883 targets all human TEAD paralogs (pan-TEAD) by binding to the TEAD lipid pocket. This allosteric binding mode blocks the interactions between YAP/TAZ coactivators and TEAD transcription factors, preventing the activation of TEAD-dependent transcription. By inhibiting TEAD, GNE-7883 suppresses the expression of genes involved in cell proliferation, survival, and oncogenesis that are driven by YAP/TAZ signaling. This makes it a valuable tool for studying YAP/TAZ-dependent cancers. |
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| ln Vitro |
GNE-7883 effectively reduces chromatin accessibility at TEAD motifs and suppresses cell proliferation in a variety of cell line models. It achieves strong antitumor efficacy in vivo. The compound's ability to overcome KRAS G12C inhibitor resistance is a notable feature, suggesting potential for combination therapies. In vitro studies have characterized its effects on TEAD-dependent transcription, cell proliferation, and YAP/TAZ activation in various cancer cell lines.
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| ln Vivo |
GNE-7883 achieves strong antitumor efficacy in vivo. It effectively overcomes KRAS G12C inhibitor resistance, suggesting potential for combination therapy with KRAS inhibitors. In vivo studies have demonstrated the compound's ability to suppress tumor growth in various cancer models. The compound's allosteric mechanism of action and pan-TEAD activity make it a promising candidate for further development as an anticancer therapeutic.
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| Enzyme Assay |
The in vitro enzyme/receptor binding (cell-free) assay for GNE-7883 typically involves a binding assay to measure its interaction with the TEAD lipid pocket. Recombinant TEAD proteins are incubated with varying concentrations of GNE-7883, and binding is measured using surface plasmon resonance (SPR), isothermal titration calorimetry (ITC), or fluorescence-based assays. Alternatively, a YAP/TAZ-TEAD protein-protein interaction assay can be performed to measure the compound's ability to disrupt the interaction between YAP/TAZ and TEAD.
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| Cell Assay |
The in vitro cellular assay for GNE-7883 typically uses cancer cell lines with active YAP/TAZ-TEAD signaling. Cells are treated with varying concentrations of GNE-7883, and TEAD-dependent transcriptional activity is measured using a TEAD-responsive luciferase reporter assay. Chromatin accessibility at TEAD motifs can be assessed using ATAC-seq or ChIP-qPCR. Cell proliferation and viability are assessed using standard assays such as CellTiter-Glo or MTT. The compound's ability to overcome KRAS G12C inhibitor resistance can be evaluated in resistant cell lines.
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| Animal Protocol |
In vivo animal studies for GNE-7883 typically involve xenograft tumor models in mice. Mice bearing subcutaneous tumors derived from cancer cell lines with YAP/TAZ-TEAD dependency or KRAS G12C inhibitor resistance are treated with GNE-7883 via oral administration at various doses, alone or in combination with KRAS inhibitors. Tumor growth inhibition is monitored over time, and at study endpoint, tumors are harvested for analysis of TEAD target gene expression, proliferation markers, and compound exposure levels.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for GNE-7883 are not extensively detailed in the available literature. The compound has a molecular weight of 500.57 and a formula of C28H29FN6O2. It is soluble in DMSO at 50 mg/mL (99.88 mM). For in vivo administration, it can be formulated as a homogeneous suspension in CMC-Na at ≥5 mg/mL for oral administration. Specific ADME parameters such as half-life, bioavailability, and clearance are not reported.
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| Toxicity/Toxicokinetics |
Toxicity data for GNE-7883 are not available in the public domain. As a research compound, comprehensive toxicological evaluations have not been performed. The compound is intended for laboratory research use only and should be handled with standard safety precautions. Appropriate personal protective equipment should be worn when handling this compound. Consult the Material Safety Data Sheet for specific safety and handling information.
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| References | |
| Additional Infomation |
5-(4-Cyclohexylphenyl)-3-(3-(fluoromethyl)azetidine-1-carbonyl)-2-(3-methylpyrazin-2-yl)pyrazolo[1,5-a]pyrimidin-7(4H)-one is an organic molecular entity.
GNE-7883 is a potent, allosteric pan-TEAD inhibitor that blocks YAP/TAZ-TEAD interactions by binding to the TEAD lipid pocket. It reduces chromatin accessibility at TEAD motifs, suppresses cell proliferation, and achieves strong antitumor efficacy in vivo. The compound effectively overcomes KRAS G12C inhibitor resistance. GNE-7883 is used to study YAP/TAZ-dependent tumors. It is not in clinical trials and has not been approved for therapeutic use. It remains a research tool for studying TEAD biology and Hippo signaling in cancer. |
| Molecular Formula |
C28H29FN6O2
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|---|---|
| Molecular Weight |
500.567269086838
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| Exact Mass |
500.233
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| CAS # |
2648450-42-2
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| PubChem CID |
164852436
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| Appearance |
White to light yellow solid powder
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| LogP |
3.8
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
37
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| Complexity |
1000
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=NC=CN=C1C2=C(C3=NC(=CC(=O)N3N2)C4=CC=C(C=C4)C5CCCCC5)C(=O)N6CC(C6)CF
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| InChi Key |
OMGKSFJZXSXHCA-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C28H29FN6O2/c1-17-25(31-12-11-30-17)26-24(28(37)34-15-18(14-29)16-34)27-32-22(13-23(36)35(27)33-26)21-9-7-20(8-10-21)19-5-3-2-4-6-19/h7-13,18-19,33H,2-6,14-16H2,1H3
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| Chemical Name |
5-(4-cyclohexylphenyl)-3-[3-(fluoromethyl)azetidine-1-carbonyl]-2-(3-methylpyrazin-2-yl)-1H-pyrazolo[1,5-a]pyrimidin-7-one
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9977 mL | 9.9886 mL | 19.9772 mL | |
| 5 mM | 0.3995 mL | 1.9977 mL | 3.9954 mL | |
| 10 mM | 0.1998 mL | 0.9989 mL | 1.9977 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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