Copanlisib-BAY-80-6946-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemECopanlisibCat. No.: HY-15346CAS No.: 1032568-63-0Synonyms: BAY 80-6946分式: CHNO分量: 480.52作靶点: PI3K作通路: PI3K/Akt/mTOR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 1M HCl : 100 mg/mL (208.11 mM; Ne

2、ed ultrasonic)DMSO : 1 mg/mL (insoluble or slightly soluble)H2O : 0.1 mg/mL (insoluble)Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.0811 mL 10.4054 mL 20.8108 mL5 mM 0.4162 mL 2.0811 mL 4.1622 mL10 mM 0.2081 mL 1.0405 mL 2.0811 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。BIOLOGICAL ACTIVIT

3、Y物活性 Copanlisib (BAY 80-6946)种 ATP竞争，选择性 I 型 PI3K 抑制剂，作于 PI3K，PI3K，PI3K 和PI3K 的 IC50 分别为 0.5，0.7，3.7 和 6.4 nM。IC50 & Target PI3K PI3K PI3K PI3K1/3 Master of Small Molecules 您边的抑制剂师www.MedChemE0.5 nM (IC50) 0.7 nM (IC50) 3.7 nM (IC50) 6.4 nM (IC50)mTOR45 nM (IC50)体外研究 Copanlisib (BAY 80-6946) potentl

4、y inhibits the catalytic activity of the class I PI3K, , , and isoforms withIC50s of 0.5, 3.7, 6.4, and 0.7 nM, respectively. Copanlisib (BAY 80-6946) shows significantly weaker activityagainst mTOR with an IC50 of 45 nM. In KPL4 cells, Copanlisib (BAY 80-6946) reduces basal levels of AKTphosphoryla

5、tion at both Thr308 and Ser473 with IC50 values of 0.4 and 0.6 nM, respectively. Copanlisib hasmean IC50 values of 19 nM against cell lines with PIK3CA-activating mutations (n = 9) and 17 nM againstHER2-positive cell lines (n=7), whereas the activity in PIK3CA wild-type and HER2-negative cells is ab

6、out40-fold less potent (average IC50=774 nM; n=11) 1.Solution: Copanlisib is dissolved in HCL and diluted with distilled water 1.体内研究 Copanlisib (BAY 80-6946) is highly efficacious in a variety of human tumor xenograft models derived fromdifferent tumor indications that exhibit an activated PI3K pat

7、hway. Copanlisib (BAY 80-6946) is administeredat 0.5 to 6 mg/kg i.v. every second day for a total of five doses starting on day 14, following tumor cellimplantation. On day 25, 3 days after the last dose, TGI rates of 77%, 84%, 99%, and 100% are observedwith Copanlisib (BAY 80-6946) at doses of 0.5,

8、 1, 3, and 6 mg/kg, respectively. Complete tumor regression isshown in 10 of 10 rats in the 3 and 6 mg/kg groups, and all rats remained tumor free at the termination of thestudy on day 73. Tumor growth delays more than 25 days are observed in the 0.5 and 1 mg/kg dose groups1.Solution: Copanlisib is

9、dissolved in a PEG400/acidified water (0.1NHCl,pH 3.5; 20/80, v/v) or 5% mannitolvehicle 1.PROTOCOLCell Assay 1 The 5 mM stock solution of Copanlisib (BAY 80-6946) (in DMSO with 10 mM trifluoroacetic acid) is used. Thecell lines are maintained in RPMI-1640 medium containing 10% heat-inactivated feta

10、l calf serum. Cellproliferation is determined using the CellTiter-Glo Luminescent Cell Viability Kit 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice and Rats 1Administration 1 The in vivo antitumor efficacy of Copanlisib (BAY 80-6946) is a

11、ssessed in athymic nude rats or nude miceusing xenograft models of human tumors. Animals are housed according to institutional guidelines withaccess to food (pelleted diet) and water ad libitum. Studies with patient-derived tumors are conducted in EPOGmbH or in Oncotest GmbH with written formed cons

12、ent from each patient and the approval from localethical committees. Tumor xenografts are generated by harvesting cells from mid-log phase cultures andinjecting subcutaneously into the right flank of each rat and mouse. Treatment is initiated when all animals inan experiment had established tumors.

13、Copanlisib (BAY 80-6946) is administered every second day, everythird day, or weekly via an intravenous bolus at the indicated doses. Tumor dimensions and body weights arerecorded twice weekly starting on the first day of treatment. Tumor volumes are calculated. Antitumor efficacyis determined as a

14、function of tumor growth inhibition (% TGI). TGI is calculated.2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEMCE has not independently confirmed the accuracy of these methods. They are for reference only.户使本产品发表的科研献 Science. 2017 Dec 1;358(6367). Blood. 2019 Jan 3;133(1):70-80. RSC Adv., 2019, 9, 6409-6418See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Liu N, et al. BAY 80-6946 is a highly selective intravenous PI3K inhibitor with potent p110 and p110 activities in tumor cell lines andxenograft models. Mol Cancer Ther. 20