AZD-0364 _ERK 抑制剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEAZD-0364Cat. No.: HY-111483CAS No.: 2097416-76-5分式: CHFNO分量: 494.5作靶点: ERK作通路: MAPK/ERK Pathway; Stem Cell/Wnt储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 100 mg/mL (202.22 mM)* means so

2、luble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.0222 mL 10.1112 mL 20.2224 mL5 mM 0.4044 mL 2.0222 mL 4.0445 mL10 mM 0.2022 mL 1.0111 mL 2.0222 mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存式和期限。体内实验 请根据您的实验动物和给药式选择适当的溶解案，配制前请先配制澄清的储备液，再依次添加助溶剂(为保证实验结果的可靠性，体内实验的作液，建议您现现

3、配，当天使；澄清的储备液可以根据储存条件，适当保存；以下溶剂前的百分 指该溶剂在您配制终溶液中的体积占)：1. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.08 mg/mL (4.21 mM); Clear solutionBIOLOGICAL ACTIVITY1/3 Master of Small Molecules 您边的抑制剂师www.MedChemE物活性 AZD-0364种有效的选择性 ERK2 抑制剂，IC50 为 0.6 nM。详细信息请参考专利献 WO2017080979A1中的化合物 example 18。IC50 & Targ

4、et ERK20.6 nM (IC50)体外研究 AZD-0364 is measured in the ERK2 mass spectrometry and A375 phospho-p90RSK assays with IC50s of 0.6nM and 5.7 nM, respectively. AZD-0364 can inhibit the growth of a panel of cancer cell lines (A549, H2122,H2009, and Calu6 cell lines) with KRAS mutations as a monotherapy and

5、this effect is synergisticallyenhanced by treatment with Selumetinib 1.体内研究 Tumor growth inhibition by AZD-0364 ethanesulfonic acid (Example 18a) in combination with MEK inhibitorSelumetinib is measured. Studies are performed in the A549 xenograft model. Selumetinib is dosed twice daily(BiD) 8 hours

6、 apart and AZD-0364 ethanesulfonic acid is dosed once daily (QD) 4 hours after the firstSelumetinib dose. Both compounds are dosed continuously for 3 weeks. Both vehicles are dosed in thevehicle group. Both Selumetinib and AZD-0364 ethanesulfonic acid reduce tumor growth relative to vehicleonly cont

7、rol. The combination of Selumetinib and AZD-0364 ethanesulfonic acid results in a reduction in tumorgrowth 1.PROTOCOLCell Assay 1 KRAS-mutant Non-Small Cell Lung Cancer (NSCLC) A549, H2122, H2009, and Calu6 cell lines are seededin 384-well black, clear bottomed plates, cultured for 18-24 hours and t

8、reated with increasing concentrationsof AZD-0364 (7.143 nM, 61 nM, 357 nM, 2.143 M and 10 M) and Selumetinib (0-10 M) in a 66 dosingmatrix. Cells are seeded at a concentration such that cells in untreated wells are approximately 80%confluent at the end of the assay. After 3 days of treatment, live c

9、ell number is determined using a SytoxGreen endpoint 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 1Administration 1 A549 is a human non small cell lung cancer line carrying an oncogenic mutation in the KRAS gene (G12S).Female nude mice

10、are implanted subcutaneously (s.c.) on the left flank, with 5106 A549 cells (ATCC) permouse.Tumor growth is monitored by twice weekly calliper measurement and volumes are calculated. Oncetumors have reached a volume of 200-300mm3 animals are randomised into groups of 7-11 and are treatedwith a conti

11、nuous combination schedule of Selumetinib (ARRY-142886) 25 mg/kg BiD and AZD-0364ethanesulfonic acid 25 mg/kg QD (four hours after first Selumetinib dose), both are dosed by peroral route.Tumor volumes are measured twice weekly after dosing commenced 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. WARD, Richard, Andrew, et al. DIHYDROIMIDAZOPYRAZINONE DERIVATIVES USEFUL IN THE TREATMENT OF CANCER.WO2017080979A1.2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEMcePdfHeightCaution: Produ