APS-2-79 |
| Catalog No.GC15240 |
APS-2-79 est un antagoniste de MEK dépendant de KSR. APS-2-79 inhibe la liaison de l'ATPbiotine À KSR2 dans le complexe KSR2-MEK1 avec une IC50 de 120 nM. APS-2-79 rend la stabilisation de l'état inactif de KSR antagonise la signalisation Ras-MAPK oncogène.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 2002381-31-7
Sample solution is provided at 25 µL, 10mM.
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IC50: 120 nM
APS-2-79 is a KSR-dependent MAPK modulator.
Kinase suppressor of Ras (KSR), a MAPK scaffold, is subject to allosteric regulation via dimerization with RAF. Targeting of KSR has important therapeutic implications for cancer, however, testing this hypothesis is difficult due to the lack of small-molecule KSR antagonists.
In vitro: APS-2-79 was found to be able to suppress KSR-stimulated MEK and ERK phosphorylation. This MAPK signalling suppression caused by APS-2-79 was dependent on direct targeting of KSR as an active site mutant, which had been demonstrated to stimulate KSR-based MAPK outputs independent of ATP-binding, which could significantly diminish the activity of APS-2-79. Moreover, the KSR-stimulated MEK phosphorylation caused by RAF was reduced by the addition of APS-2-79 markedly. In addition, APS-2-79 was no effetive when KSR was absent or when the KSR2(A690F) mutant was used for in vitro assays, indicating that the activity of APS-2-79 was from direct targeting of KSR. However, APS-2-79 was found to lack direct activity against the highly homologous active RAF family kinases, such as recombinant BRAF and CRAF, or cellular BRAF(V600E) [1].
In vivo: So far, there is no animal in vivo data reported.
Clinical trial: Up to now, APS-2-79 is still in the preclinical development stage.
Reference:
[1] Dhawan NS, Scopton AP, Dar AC. Small molecule stabilization of the KSR inactive state antagonizes oncogenic Ras signalling. Nature. 2016 Sep 1;537(7618):112-116.
Cell experiment: | Cell viability assays are performed in 96 well plates. Optimal cell densities for 96 well plate assays are determined to obtain linear growth over the time course of assays. 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 with inhibitors (e.g., APS-2-79; 100-3,000 nM) for 72hrs before measuring viability. H2087 and HEPG2 cells are plated at 2000 cells per well, and treated with inhibitors (e.g., APS-2-79; 100-3,000 nM) for 72hrs. Cell viability is measured using Resazurin, and the percent cell viability is determined by normalizing inhibitor-treated samples to DMSO controls[1]. |
References: [1]. Dhawan NS, et al. Small molecule stabilization of the KSR inactive state antagonizes oncogenic Ras signalling. Nature. 2016 Aug 24;537(7618):112-116. | |
| Cas No. | 2002381-31-7 | SDF | |
| Chemical Name | 6,7-dimethoxy-N-(2-methyl-4-phenoxyphenyl)quinazolin-4-amine hydrochloride | ||
| Canonical SMILES | CC1=CC(OC2=CC=CC=C2)=CC=C1NC3=C4C=C(OC)C(OC)=CC4=NC=N3.[H]Cl | ||
| Formula | C23H22ClN3O3 | M.Wt | 423.89 |
| Solubility | DMF: 10 mg/mL,DMSO: 25 mg/mL,DMSO:PBS (pH 7.2) (1:2): 0.3 mg/mL,Ethanol: 1 mg/mL | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.3591 mL | 11.7955 mL | 23.591 mL |
| 5 mM | 0.4718 mL | 2.3591 mL | 4.7182 mL |
| 10 mM | 0.2359 mL | 1.1796 mL | 2.3591 mL |
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Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
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Quality Control & SDS
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- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
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Average Rating: 5 (Based on Reviews and 8 reference(s) in Google Scholar.)
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