1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemERociletinibCat. No.: HY-15729CAS No.: 1374640-70-6Synonyms: CO-1686; AVL-301; CNX-419分式: CHFNO分量: 555.55作靶點(diǎn): EGFR作通路: JAK/STAT Signaling; Protein Tyrosine Kinase/RTK儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C

2、1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 43 mg/mL (77.40 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 1.8000 mL 9.0001 mL 18.0002 mL5 mM 0.3600 mL 1.8000 mL 3.6000 mL10 mM 0.1800 mL 0.9000 mL 1.8000 mL請(qǐng)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(qǐng)注意儲(chǔ)備液的保存式和期限。BIOLOGICAL ACTIVITY物活性

3、Rociletinib (CO-1686)種可服的 EGFR 抑制劑，能夠抑制 EGFRL858R/T790M 和 EGFRWT 的活性，IC50值分別為 21.5 nM 和 303.3 nM。IC50 & Target EGFRL858R/T790M EGFRT790M21.5 nM (Ki) 303.3 nM (Ki)1/2 Master of Small Molecules 您邊的抑制劑師www.MedChemE體外研究 Rociletinib (CO-1686) (0.1 M) inhibits EGFR potently and irreversibly, and inhibits

4、more than 50% of 23targets. Rociletinib potently and selectively inhibits growth of NSCLC cells expressing mutant EGFR andinduces apoptosis. Rociletinib resistant NSCLC cell lines are sensitive to AKT inhibition 1.體內(nèi)研究 Rociletinib (CO-1686) (100 mg/kg/day, p.o.) demonstrates anti-tumor activity in N

5、SCLC EGFR mutantxenograft models. Rociletinib (CO-1686) (50 mg/kg bid, p.o.) demonstrates anti-tumor activity in humanEGFR-L858R and EGFR-L858R-T790M expressing transgenic mice 1.PROTOCOLCell Assay 1 Cells are seeded at 3,000 cells/well in growth media supplemented with 5% FBS, 2 mM L-glutamine, and

6、 1% P/S, allowed to adhere overnight, and treated with a dilution series of test compound (Rociletinib) for 72 hr.Cell viability is determined by CellTiter Glo and results are represented as background-subtracted relativelight units normalized to a DMSO-treated control. Growth inhibition (GI50) valu

7、es are determined byGraphPad Prism 5.04. Combination index (CI) data is generated using CalcuSyn.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Briefly, NCr nu/nu mice are sub-cutaneously implanted with 1107 tumor cells in 50% Matrigel (injectio

8、nAdministration 1 volume of 0.2 mL/mouse). Once tumors reached 100-200 mm3, Animals are dosed with compounds(Rociletinib) as outlined (N=10 animals/gp). Briefly, LUM1686 PDX tumor fragments, harvested from donormice, are inoculated into BALB/c nude mice. Administration of test compounds (Rociletinib

9、 (CO-1686) isinitiated at a mean tumor size of approximately 160 mm3. Tumor growth is monitored over time to determinetumor growth inhibition of the experimental agent vs. vehicle. The endpoint of the experiment is a meantumor volume (MTV) in control group of 2000 mm3. Percent TGI is defined as the

10、difference between theMTV of the designated control group and the MTV of the drug-treated group, expressed as a percentage ofthe MTV of the designated control group. Data is presented as meanstandard error of the mean (SEM).MCE has not independently confirmed the accuracy of these methods. They are

11、for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Science. 2017 Dec 1;358(6367). J Med Chem. 2017 Apr 13;60(7):2944-2962. Mol Cancer Ther. 2018 Mar;17(3):603-613. ChemMedChem. 2017 Nov 22;12(22):1857-1865. Patent. US20190010159A1.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Walter AO, et al. Discovery of a mutant-selective covalent inhibitor of EGFR that overcomes T790M-mediated resistance in NSCLC.Cancer Discov. 2013 Sep 25.McePdfHeight2/2 Master of Small Molecules 您邊的抑制劑師www.MedChemECaution: Product