ARS-853 - Ras 抑制劑 - 生命科學(xué)試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEARS-853Cat. No.: HY-19706CAS No.: 1629268-00-3分式: CHClNO分量: 432.94作靶點(diǎn): Ras作通路: GPCR/G Protein儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 71 mg/mL (164.00 mM)* means soluble, but saturat

2、ion unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 2.3098 mL 11.5489 mL 23.0979 mL5 mM 0.4620 mL 2.3098 mL 4.6196 mL10 mM 0.2310 mL 1.1549 mL 2.3098 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲(chǔ)備液，并請注意儲(chǔ)備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 ARS-853是選擇性,共價(jià)的 KRASG12C 抑制劑，IC50 為2.5 M。IC50 & Target KRAS(G12C)2.5 M

3、 (IC50)體外研究ARS853 is designed to bind KRASG12C with high affinity. Treatment of KRASG12C-mutant lung cancer cells1/2 Master of Small Molecules 您邊的抑制劑師www.MedChemEwith ARS853 reduces the level of GTP-bound KRAS by more than 95% (10 M). ARS853 inhibitsproliferation with an inhibitory concentration 50%

4、 (IC50) of 2.5 M, which is similar to its IC50 for targetinhibition. ARS853 (10 M) inhibits effector signaling and cell proliferation to varying degrees in sixKRASG12C mutant lung cancer cell lines, but not in non-KRASG12C models. Similarly, it completelysuppresses the effects of exogenous KRASG12C

5、expression on KRAS-GTP levels, KRAS-BRAF interaction,and ERK signaling. ARS-853 treatment also induces apoptosis in four KRASG12C mutant cell lines. ARS853selectively reduces KRAS-GTP levels and RAS-effector signaling in KRASG12C-mutant cells, while inhibitingtheir proliferation and inducing cell de

6、ath 1. ARS-853 inhibits mutant KRAS-driven signaling by binding tothe GDP-bound oncoprotein and preventing activation 2.PROTOCOLKinase Assay 1 Purified KRAS (1 M) is incubated EDTA (10 mM) and GDP (1 mM) or GTPS (1 mM) at room temperaturefor 1 h followed by addition of MgCl2 (1 mM) to terminate the

7、reaction. ARS853 (1 M) is then added and themixture is incubated for another hour at room temperature. HEK293 cells expressing various KRAS mutantsare treated with ARS853. Proteins are extracted using a buffer containing 9M urea, 10 mM DTT and 50 mMammonium bicarbonate, pH 8, heated to 65C for 15 mi

8、n and alkylated using 50 mM iodoacetamide at 37Cfor 30 min. The samples are desalted by gel filtration in Zeba spin desalting plates followed by addition ofsequencing-grade trypsin to a concentration of 10 g/ml, and incubation for one hour at 37C. Heavy isotopicstandards (25 fmol) of the KRASG12C ta

9、rget peptide and KRAS normalization peptide are added to thesamples followed by desalting in Strata-X polymeric reverse phase plates. LC-MS/MS analysis is performedin a Q Exactive quadrupole orbitrap mass spectrometer under standard condition. The amount ofKRASG12C bound by the drug is determined by

10、 the ratio of the modified G12C peptide to that of the heavyisotopic standards 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Lito P, et al. Allele-specific inhibitors inactivate mutant KRAS G12C by a trapping mechanism. Science. 2016 Feb 5;351(6273):604-8.2. Patricelli MP, et al. Selective Inhibition of Oncogenic KRAS Output with Small Molecules Targeting the Inactive State. Cancer Discov.2016 Mar;6(3):316-29.McePdfHeightCaution: Product has not been f