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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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Purity: ≥98%
APS-2-79 HCl (APS279 HCl; APS-279), the hydrochloride salt of APS-2-79, is an antagonist of MAPK (mitogen-activated protein kinase) with anticancer effects. By inhibiting RAF heterodimerization and the conformational alterations necessary for the phosphorylation and activation of KSR-bound MEK, it modifies KSR-dependent MAPK signaling. It was discovered that APS-2-79 could prevent MEK and ERK phosphorylation that was induced by the KSR. 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 |
ERK2 (IC50 = 8.8 nM); MEK1
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| ln Vitro |
Through direct binding to the KSR active site, APS-2-79 performs as an antagonist of RAF's phosphorylation of MEK. When KSR is absent or when the KSR2(A690F) mutant is utilized for in vitro assays, APS-2-79 is inactive. By inhibiting the release of negative feedback signaling, APS-2-79 enhances the potency of several MEK inhibitors in particular within Ras-mutant cell lines[1].
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| ln Vivo |
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| Enzyme Assay |
APS-2-79 has kinase suppressor of Ras (KSR)-dependent antagonistic actions against RAF-mediated MEKphosphorylation. The KSR2-MEK1 complex's IC50 for KSR2 is 120±23 nM, and APS-2-79 binds to KSR2 directly within it.
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| 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 specifically plated at 500 cells per well and subjected to inhibitor treatments for 72 hours prior to viability measurements. 2000 cells per well of H2087 and HEPG2 cells are plated, and inhibitors are applied for 72 hours. Resazurin is used to measure cell viability, and the percentage of cell viability is calculated by comparing inhibitor-treated samples to DMSO controls.
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| Animal Protocol |
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| References |
| Molecular Formula |
C23H22CLN3O3
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| Molecular Weight |
423.8921
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| Exact Mass |
423.134
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| Elemental Analysis |
C, 65.17; H, 5.23; Cl, 8.36; N, 9.91; O, 11.32
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| CAS # |
2002381-31-7
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| Related CAS # |
APS-2-79;2002381-25-9
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| PubChem CID |
122177134
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| Appearance |
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 |
6
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| Heavy Atom Count |
30
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| Complexity |
502
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
LIXKSHWZJNNZHG-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H21N3O3.ClH/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);1H
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| Chemical Name |
6,7-dimethoxy-N-(2-methyl-4-phenoxyphenyl)quinazolin-4-amine;hydrochloride
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| Synonyms |
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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 |
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| 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) |
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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 | 2.3591 mL | 11.7955 mL | 23.5910 mL | |
| 5 mM | 0.4718 mL | 2.3591 mL | 4.7182 mL | |
| 10 mM | 0.2359 mL | 1.1796 mL | 2.3591 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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