Prexasertib-LY2606368-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEPrexasertibCat. No.: HY-18174CAS No.: 1234015-52-1Synonyms: LY2606368分式: CHNO分量: 365.39作靶点: Checkpoint Kinase (Chk)作通路: Cell Cycle/DNA Damage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 :

2、60 mg/mL (164.21 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.7368 mL 13.6840 mL 27.3680 mL5 mM 0.5474 mL 2.7368 mL 5.4736 mL10 mM 0.2737 mL 1.3684 mL 2.7368 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 ACTIVITY物活性 Prexasertib (LY2606368

3、)种有效，选择性， ATP 竞争性的 Chk1 抑制剂，Ki 和 IC50 分别为 1 nM 和 0.9nM。IC50 & Target Chk1 Chk1 Chk20.9 nM (Ki) 50) 8 nM (IC50)1/3 Master of Small Molecules 您边的抑制剂师www.MedChemE体外研究 Prexasertib (LY2606368) is a potent and selective ATP competitive inhibitor of Chk1, with an IC50 of 50 of 8nM. Prexasertib has an EC50

4、of 1 nM for CHK1 activity through autophosphorylation of serine 296 and 50 of9 nM. However, 100 nM Prexasertib does not inhibit PMA-stimulated RSK but instead weakly stimulatesphosphorylation of S6 on serines 235/236. Prexasertib is broadly antiproliferative with IC50s of 3 nM, 3 nM,10 nM, 37 nM, an

5、d 68 nM against U-2 OS, Calu-6, HT-29, HeLa, and NCI-H460 cell lines, respectively.Prexasertib (4 nM) results in a large shift in cell-cycle populations from G1 and G2-M to S-phase with anaccompanied induction of H2AX phosphorylation in U-2 OS cells 1. Prexasertib (LY2606368; 25 M)exhibits inhibitor

6、y activities against proliferation of AGS and MKN1 cells. Prexasertib (20 nM) inhibits HRrepair capacity DR-GFP cells. Prexasertib (5 nM) in combination with PARP inhibitor BMN673, displayssynergistic anticancer effects in gastric cancer cells 2.体内研究 Prexasertib (LY2606368; 15 mg/kg, s.c.) significa

7、ntly inhibits tumor growth in xenograft tumor models withless animal weight loss 1. Prexasertib (LY2606368; 2 mg/kg, s.c.) and BMN673 combination has synergisticanticancer effect in gastric cancer PDX model, and the effect is higher than that of one drug alone 2.PROTOCOLCell Assay 2 Proliferation in

8、hibition effect of Chk1 ablation, IR sensitivity, anticancer effect of BMN673 and Prexasertib aredetected by MTS Cell Proliferation Colorimetric Assay Kit. Cells are seeded into 96 wells cell culture plate,then treated with indicated experiment conditions, then added 20 L MTS reagent to each well su

9、bsequently,after incubated for 2 hours, cell viability of each well is detected on microplate reader at a wavelength of 490nM 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Female CD-1 nu-/nu- mice (26-28 g) are used for this study. Tumor grow

10、th is initiated by subcutaneousAdministration 1 injection of 1106 Calu-6 cells in a 1:1 mixture of serum-free growth medium and Matrigel in the rear flank ofeach subject animal. When tumor volumes reach approximately 150 mm3 in size, the animals arerandomized by tumor size and body weight, and place

11、d into their respective treatment groups. Vehicleconsisting of 20% Captisol pH4 or Prexasertib is administered by subcutaneous injection in a volume of 200L. Four, eight, 12, 24, and 48 hours after drug administration, blood for plasma drug exposure is extractedvia cardiac puncture and assayed on a

12、Sciex API 4000 LC/MS-MS system. The xenograft tissue is promptlyremoved and prepared. Lysates are analyzed by immunoblot analysis for protein phosphorylation levels.Group means, SEs and P values are calculated using Kronos.MCE has not independently confirmed the accuracy of these methods. They are f

13、or reference only.户使本产品发表的科研献 Nat Commun. 2019 Aug 2;10(1):3485. Mol Cancer Res. 2019 Jul 23. pii: molcanres.0381.2019. Methods Mol Biol. 2018;1711:351-398.See more customer validations on HYPERLINK / www.MedChemE2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEREFERENCES1. King C, et al. LY2606368 Causes Replication Catastrophe and Antitumor Effects through CHK1-Dependent Mechanisms. Mol CancerTher. 2015 Sep;14(9):2004-12. Yin Y, et al. Chk1 inhibition potentiates the therapeutic efficacy of PARP inhibitor BMN673 in gastric cancer. Am J Cancer Res. 2017Mar 1;7(3):4