| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg | |||
| Other Sizes |
| Targets |
The primary targets of YAP/TAZ inhibitor-1 are YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif), which are transcriptional co-activators of the Hippo signaling pathway. The Hippo pathway regulates organ size, tissue regeneration, and tumor suppression. YAP and TAZ are key downstream effectors that promote cell proliferation and survival when activated. YAP/TAZ inhibitor-1 inhibits YAP and TAZ with an IC₅0 of less than 0.100 microM, blocking their transcriptional activity and downstream gene expression. By inhibiting YAP and TAZ, the compound suppresses cell proliferation and has significant anti-proliferative effects.
|
|---|---|
| ln Vitro |
The Hippo pathway network's transcriptional coactivators, YAP and TAZ, control cell division, migration, and apoptosis. The transcriptional coactivator with PDZ binding motif/Yes-associated protein transcriptional coactivator (TAZ/YAP) is inhibited by YAP/TAZ inhibitor-1.
In vitro studies demonstrate that YAP/TAZ inhibitor-1 is a potent inhibitor of YAP and TAZ with an IC₅0 of less than 0.100 microM in a firefly luciferase assay. The compound exhibits significant cellular anti-proliferative effects, making it a valuable tool for studying the Hippo pathway and its role in cancer and tissue regeneration. YAP/TAZ inhibitor-1 is extracted from patent WO2017058716A1, Compound 1. Its potent inhibitory activity makes it useful for validating YAP and TAZ as therapeutic targets in various cancers where Hippo pathway dysregulation plays a role. |
| ln Vivo |
In vivo studies of YAP/TAZ inhibitor-1 are limited, as it is primarily used as a research tool in cellular assays. However, given its potent inhibition of YAP and TAZ with an IC₅0 of less than 0.100 microM and its anti-proliferative effects, the compound may have potential for in vivo efficacy studies in animal models of cancers where YAP and TAZ are dysregulated. Further studies are needed to evaluate its pharmacokinetic properties, bioavailability, and efficacy in vivo. The compound may also be useful for studying the role of the Hippo pathway in tissue regeneration and development.
|
| Enzyme Assay |
For in vitro enzyme/receptor binding assays, YAP/TAZ inhibitor-1 can be evaluated using biochemical assays that measure the interaction between YAP/TAZ and their binding partners, such as TEAD transcription factors. The compound is incubated with recombinant proteins at various concentrations, and the disruption of YAP/TAZ-TEAD interactions is quantified using AlphaScreen, TR-FRET, or co-immunoprecipitation assays. IC₅0 values are determined from dose-response curves. Binding affinity can be assessed using surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC). Standard assay conditions include physiological buffer systems with appropriate pH and ionic strength.
|
| Cell Assay |
For in vitro cellular experiments, YAP/TAZ inhibitor-1 is tested in cell lines with active YAP/TAZ signaling to evaluate its effects on cell proliferation and gene expression. Cells are cultured in appropriate media and treated with various concentrations of the compound (typically ranging from nanomolar to micromolar). YAP/TAZ transcriptional activity is assessed using luciferase reporter assays or by measuring the expression of YAP/TAZ target genes by qPCR. Cell proliferation is assessed using MTT, CellTiter-Glo, or colony formation assays. Cell cycle analysis and apoptosis assays are performed. The compound's effects on cell migration and invasion can also be assessed.
|
| Animal Protocol |
For in vivo animal experiments, YAP/TAZ inhibitor-1 can be administered to animals via various routes including oral gavage, intravenous injection, or intraperitoneal injection, depending on its solubility and pharmacokinetic properties. The compound's efficacy can be evaluated in tumor models where YAP/TAZ signaling is activated. Typical dosing regimens may range from 1 to 50 mg/kg administered daily or intermittently. Tumor volume is measured regularly, and tumor growth inhibition is calculated. Pharmacodynamic markers such as YAP/TAZ target gene expression are measured in tumors. Body weight and overall health are monitored.
|
| ADME/Pharmacokinetics |
Pharmacokinetic properties of YAP/TAZ inhibitor-1 are not extensively detailed in the public literature. As a small molecule with a molecular weight of 621.81 g/mol, it may have reasonable oral bioavailability and tissue distribution. The presence of sulfur and the lipophilic nature of the compound may influence its metabolic stability and clearance. Detailed parameters such as Cₘₐₓ, Tₘₐₓ, AUC, half-life, and clearance would need to be determined through comprehensive PK studies. The compound's protein binding, metabolism, and excretion pathways remain to be fully characterized. Formulation development may be necessary for optimal in vivo administration.
|
| Toxicity/Toxicokinetics |
Toxicological data for YAP/TAZ inhibitor-1 are limited, as it is primarily a research tool. As an inhibitor of YAP and TAZ, its toxicity would depend on the importance of the Hippo pathway for normal tissue homeostasis and regeneration. YAP and TAZ play critical roles in organ size control, tissue repair, and stem cell function. Their inhibition could have significant effects on normal tissues. Comprehensive toxicology studies would be needed for further development. Appropriate safety precautions should be taken when handling this compound, including the use of personal protective equipment and adherence to institutional safety guidelines.
|
| References | |
| Additional Infomation |
YAP/TAZ inhibitor-1 is a research compound used to study the Hippo signaling pathway. No clinical trials or regulatory approvals have been reported for this compound as a therapeutic agent. It is available from various chemical suppliers for research purposes only. The compound is a YAP/TAZ inhibitor extracted from patent WO2017058716A1, Compound 1, with an IC₅0 of less than 0.100 microM in a luciferase assay and significant cellular anti-proliferative effects.
|
| Molecular Formula |
C33H39N3O5S2
|
|---|---|
| Molecular Weight |
621.8099
|
| Exact Mass |
621.233
|
| CAS # |
2093565-23-0
|
| PubChem CID |
138377547
|
| Appearance |
Off-white to yellow solid powder
|
| LogP |
5.9
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
8
|
| Rotatable Bond Count |
6
|
| Heavy Atom Count |
43
|
| Complexity |
1220
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
S(C1C([H])=C([H])C2C3C([H])=C([H])C(=C([H])C=3/C(/C=2C=1[H])=N/O[H])S(N1C([H])([H])C([H])([H])N(C([H])(C([H])([H])[H])C2C([H])=C([H])C([H])=C([H])C=2[H])C([H])([H])C1([H])[H])(=O)=O)(C1([H])C([H])([H])C([H])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])C1([H])[H])(=O)=O
|
| InChi Key |
MYVLNSCWZUAUMQ-NWBJSICCSA-N
|
| InChi Code |
InChI=1S/C33H39N3O5S2/c1-23(24-7-5-4-6-8-24)35-17-19-36(20-18-35)43(40,41)27-10-12-29-28-11-9-26(21-30(28)32(34-37)31(29)22-27)42(38,39)25-13-15-33(2,3)16-14-25/h4-12,21-23,25,37H,13-20H2,1-3H3/b34-32+
|
| Chemical Name |
(NE)-N-[2-(4,4-dimethylcyclohexyl)sulfonyl-7-[4-(1-phenylethyl)piperazin-1-yl]sulfonylfluoren-9-ylidene]hydroxylamine
|
| 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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : ~62.5 mg/mL (~100.51 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.02 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 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. Solubility in Formulation 2: 2.5 mg/mL (4.02 mM) in 10% DMSO + 90% (20% SBE-β-CD in 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 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: 2.5 mg/mL (4.02 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6082 mL | 8.0410 mL | 16.0821 mL | |
| 5 mM | 0.3216 mL | 1.6082 mL | 3.2164 mL | |
| 10 mM | 0.1608 mL | 0.8041 mL | 1.6082 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
