| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 50mg |
|
||
| Other Sizes |
|
K-975 (K975) is the first covalent TEAD inhibitor that disrupt YAP/TAZ-TEAD protein-protein interaction, thus showing anticancer activity. K-975 acts by covalently binding to an internal cysteine residue located in the palmitate-binding pocket of TEAD.
| ln Vitro |
Cell proliferation in malignant pleural mesothelioma (MPM) cell lines lacking NF2 is inhibited by K-975 (0.1–10,000 nM; 144 h) [1]. In NCI-H226 cells, the protein-protein interaction (PPI) between Halo-YAP and endogenous TEAD1/4 as well as Halo-TAZ and TEAD1/4 is inhibited by K-975 (10–10,000 nM; 24 hours) [1]. K-975 (0.1-10000 nM; 24 h) does not reduce reporter gene activity in NCI-H661/NRF2-Luc cells, but it significantly suppresses reporter gene activity in NCI-H661/CTGF-Luc cells, with a maximum inhibition of around 70%. [1]. In NCI-H226 cells, K-975 (1–10,000 nM; 24 hours) decreases the expression of NPPB, CTGF, and IGFBP3 mRNA and enhances the expression of FBXO32 mRNA [1].
|
|---|---|
| ln Vivo |
K-975 (10-300 mg/kg; given orally twice daily for 14 days) reduces tumor growth by decreasing YAP1/TAZ-TEAD signaling in an MPM xenograft mice model [1].
|
| Cell Assay |
Cell proliferation experiment [1]
Cell Types: MPM that does not express NF2 and malignant MPM that expresses NF2 Cell Tested Concentrations: 0.1, 1, 10, 100, 1000, 10000 nM Incubation Duration: 144 hrs (hours) Experimental Results: Strong inhibitory effect on NF2-non Expressing cell lines are higher than those expressing NF2. Inhibits the proliferation of MSTO-211H cells, an NF2-expressing cell line. Western Blot Analysis[1] Cell Types: NCI-H226 Cell Tested Concentrations: 10, 100, 1000, 10000 nM Incubation Duration: 24 hrs (hours) Experimental Results: TEAD1-YAP1 PPI and TEAD4-YAP1 PPI were inhibited. Inhibits TEAD1-TAZ PPI and TEAD4-TAZ PPI. |
| Animal Protocol |
Animal/Disease Models: Male SCID (severe combined immunodeficient) mouse (5 weeks) injected with NCI-H226 or MSTO-211H cells [1]
Doses: 10, 30, 100, 300 mg/kg Route of Administration: Orally twice (two times) daily for 14 days Experimental Results: Performance Tumor effects in potent anti-MPM sc xenograft mouse models. diminished expression of CTGF, IGFBP3, and NPPB, and increased expression of FBXO32 in the NCI-H226 xenograft model. |
| References |
| Molecular Formula |
C16H14CLNO2
|
|---|---|
| Molecular Weight |
287.7409
|
| Exact Mass |
287.071
|
| CAS # |
2563855-03-6
|
| PubChem CID |
155353714
|
| Appearance |
White to off-white solid powder
|
| LogP |
4.2
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
2
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
20
|
| Complexity |
339
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
ClC1C([H])=C([H])C(=C([H])C=1[H])OC1C([H])=C(C([H])=C([H])C=1C([H])([H])[H])N([H])C(C([H])=C([H])[H])=O
|
| InChi Key |
KPXAHQSIROUBPH-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C16H14ClNO2/c1-3-16(19)18-13-7-4-11(2)15(10-13)20-14-8-5-12(17)6-9-14/h3-10H,1H2,2H3,(H,18,19)
|
| Chemical Name |
N-[3-(4-chlorophenoxy)-4-methylphenyl]prop-2-enamide
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~220 mg/mL (~764.58 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 5.5 mg/mL (19.11 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 sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 55.0 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: ≥ 5.5 mg/mL (19.11 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 55.0 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: ≥ 5.5 mg/mL (19.11 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.4754 mL | 17.3768 mL | 34.7536 mL | |
| 5 mM | 0.6951 mL | 3.4754 mL | 6.9507 mL | |
| 10 mM | 0.3475 mL | 1.7377 mL | 3.4754 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
