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DEL-22379
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
DEL-22379图片
CAS NO:181223-80-3
规格:≥98%
包装与价格:
包装价格(元)
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议
500mg电议

产品介绍
理化性质和储存条件
Molecular Weight (MW)444.53
FormulaC26H28N4O3
CAS No.181223-80-3
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: 89 mg/mL (200.2 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Other info

Chemical Name: (E)-N-(3-((5-methoxy-1H-indol-3-yl)methylene)-2-oxoindolin-5-yl)-3-(piperidin-1-yl)propanamide

InChi Key: INQUULPXCZAKMS-LPYMAVHISA-N

InChi Code: InChI=1S/C26H28N4O3/c1-33-19-6-8-23-20(15-19)17(16-27-23)13-22-21-14-18(5-7-24(21)29-26(22)32)28-25(31)9-12-30-10-3-2-4-11-30/h5-8,13-16,27H,2-4,9-12H2,1H3,(H,28,31)(H,29,32)/b22-13+

SMILES Code: O=C(NC1=CC2=C(NC(/C2=C/C3=CNC4=C3C=C(OC)C=C4)=O)C=C1)CCN5CCCCC5

SynonymsDEL 22379; DEL22379; DEL-22379.
实验参考方法
In Vitro

In vitro activity: DEL-22379 inhibits ERK dimerization without affecting its phosphorylation. In a panel of human cell lines harboring mutant BRAF (V600E) or RAS (Q61L or G12V), DEL-22379 shows potent anti-proliferative effects, and induces apoptosis.


Kinase Assay: Compound screening is performed in HEK293T cells treated with the potential inhibitors (10 μM) for 30 min before EGF stimulation. Cellular lysates are tested for ERK dimerization by native PAGE and p-ERK evaluation of the potential positives. In vitro ERK dimerization is assayed using GST-MEK1 ΔN EE purified from bacteria, bound to glutathione sepharose beads, and incubated with 25 μg/ml of purified His-ERK2 plus increasing concentrations of DEL-22379. Western blotting, kinase assays, and luciferase assays are also performed. In silico docking of the DEL-22379 compound is carried out with the modeling tools provided by the OpenEye package (v. 2.1).


Cell Assay: Cellular proliferation is analyzed by Alamar blue assays. Briefly, Cells (A panel of human cell lines harboring mutant BRAF (V600E) or RAS (Q61L or G12V)) are plated in 96-well plates at a density of 1000-2000 cells per well. Cells are treated with drug concentrations prepared by serial dilution ranging from 0.1 nM to 10 μM. 48 hr after drug treatment cells are exposed to Alamar Blue and the colorimetric change is measured at 570 and 600 nm. GI50 is estimated by nonlinear regression using GraphPad5 Prism Software.

In VivoDEL-22379 (15 mg/kg, i.p.) prevents tumor growth and metastasis in mice bearing A375 (BRAF mutant) and HCT116 (KRAS mutant) tumors, but fails to prevent the formation of tumors in mice injected with CHL cells (WT/WT).
Animal modelNude mice bearing A375 (BRAF mutant), CHL (WT/WT) or HCT116 (KRAS mutant) tumors
Formulation & DosageDissolved in 1% DMSO; 15 mg/kg; i.p.
References

Cancer Cell. 2015 Aug 10;28(2):170-82.

生物活性


Identification and Validation of DEL-22379 as an ERK Dimerization Inhibitor. Cancer Cell. 2015 Aug 10;28(2):170-82.



Antitumor Effects of DEL-22379 in Mice. Cancer Cell. 2015 Aug 10;28(2):170-82.