| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg |
|
||
| Other Sizes |
|
APS-2-79 (APS-279) is a potent antagonist of MAPK (mitogen-activated protein kinase) with antitumor activity. It influences KSR-dependent MAPK signaling by inhibiting RAF heterodimerization and the conformational alterations necessary for phosphorylating and activating KSR-bound MEK. KSR-induced phosphorylation of MEK and ERK was found to be suppressed by APS-2-79. The direct targeting of KSR as an active site mutant by APS-2-79, which has been shown to stimulate KSR-based MAPK outputs independently of ATP-binding, was necessary for the MAPK signaling suppression that APS-2-79 caused. This direct targeting of KSR could significantly reduce the activity of APS-2-79. Additionally, the addition of APS-2-79 significantly decreased the RAF-caused KSR-stimulated MEK phosphorylation. APS-2-79 may be used as a treatment option for Ras-driven cancers and has the potential to enhance the effectiveness of current MAPK inhibitors.
| Targets |
MEK1; KSR2 (IC50 = 120 nM)
|
||
|---|---|---|---|
| ln Vitro |
APS-2-79 (5 μM) suppresses KSR-stimulated MEK and ERK phosphorylation in 293H cells[1].
APS-2-79 (1 μM) enhances the clinical MEK inhibitor trametinib's effectiveness in cancer cell lines with K-Ras mutations.[1] |
||
| ln Vivo |
|
||
| Enzyme Assay |
APS-2-79 acts as an antagonist of RAF-mediated MEKphosphorylation and a kinase suppressor of Ras (KSR)-dependent. With an IC50 for KSR2 of 120±23 nM, APS-2–79 binds specifically to KSR2 within the KSR2-MEK1 complex.
|
||
| Cell Assay |
In 96-well plates, cell viability assays are carried out. In order to achieve linear growth over the course of the assays, the optimal cell densities for 96-well plate assays are identified. A549, HCT-116, A375, SK-MEL-239, COLO-205, LOVO, SK-MEL-2, CALU-6, MEWO, SW620, and SW1417 cells are plated at 500 cells per well and treated for 72 hours with inhibitors (e.g., APS-2-79; 100-3,000 nM) before viability measurements are taken. 2000 H2087 and HEPG2 cells are plated in wells, and they are then exposed to inhibitors (such as APS-2-79; 100–3,000 nM) for 72 hours. Resazurin is used to measure cell viability, and the percent of viable cells is calculated by comparing inhibitor-treated samples to DMSO controls[1].
|
||
| Animal Protocol |
|
||
| References |
| Molecular Formula |
C23H21N3O3
|
|
|---|---|---|
| Molecular Weight |
387.44
|
|
| Exact Mass |
387.158
|
|
| Elemental Analysis |
C, 71.30; H, 5.46; N, 10.85; O, 12.39
|
|
| CAS # |
2002381-25-9
|
|
| Related CAS # |
APS-2-79 hydrochloride;2002381-31-7
|
|
| PubChem CID |
121499159
|
|
| Appearance |
White to off-white solid powder
|
|
| Density |
1.2±0.1 g/cm3
|
|
| Boiling Point |
528.6±50.0 °C at 760 mmHg
|
|
| Flash Point |
273.5±30.1 °C
|
|
| Vapour Pressure |
0.0±1.4 mmHg at 25°C
|
|
| Index of Refraction |
1.656
|
|
| LogP |
5.36
|
|
| Hydrogen Bond Donor Count |
1
|
|
| Hydrogen Bond Acceptor Count |
6
|
|
| Rotatable Bond Count |
6
|
|
| Heavy Atom Count |
29
|
|
| Complexity |
502
|
|
| Defined Atom Stereocenter Count |
0
|
|
| SMILES |
O(C1C([H])=C([H])C([H])=C([H])C=1[H])C1C([H])=C([H])C(=C(C([H])([H])[H])C=1[H])N([H])C1C2=C([H])C(=C(C([H])=C2N=C([H])N=1)OC([H])([H])[H])OC([H])([H])[H]
|
|
| InChi Key |
PEKZLFZZBGBOPJ-UHFFFAOYSA-N
|
|
| InChi Code |
InChI=1S/C23H21N3O3/c1-15-11-17(29-16-7-5-4-6-8-16)9-10-19(15)26-23-18-12-21(27-2)22(28-3)13-20(18)24-14-25-23/h4-14H,1-3H3,(H,24,25,26)
|
|
| Chemical Name |
6,7-dimethoxy-N-(2-methyl-4-phenoxyphenyl)quinazolin-4-amine
|
|
| Synonyms |
|
|
| 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) |
|
|||
|---|---|---|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2 mg/mL (5.16 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 20.0 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 mg/mL (5.16 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 20.0 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 mg/mL (5.16 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 | 2.5810 mL | 12.9052 mL | 25.8104 mL | |
| 5 mM | 0.5162 mL | 2.5810 mL | 5.1621 mL | |
| 10 mM | 0.2581 mL | 1.2905 mL | 2.5810 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
