YM-155-Sepantronium-bromide-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEYM-155Cat. No.: HY-10194CAS No.: 781661-94-7Synonyms: Sepantronium bromide分式: CHBrNO分量: 443.29作靶点: Survivin; Autophagy作通路: Apoptosis; Autophagy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、: 10.66 mg/mL (24.05 mM; Need ultrasonic and warming)Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.2559 mL 11.2793 mL 22.5586 mL5 mM 0.4512 mL 2.2559 mL 4.5117 mL10 mM 0.2256 mL 1.1279 mL 2.2559 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，配制前请先配制澄的储备液，再依次添加助溶剂(为保证

3、实验结果的可靠性，体内实验的作液，建议您现现配，当天使；澄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 40% PEG300 5% Tween-80 45% salineSolubility: 2 mg/mL (4.51 mM); Clear solutionBIOLOGICAL ACTIVITY1/3 Master of Small Molecules 您边的抑制剂师www.MedChemE物活性 YM-155survivin 抑制剂，IC50为0.54 nM。IC50 & Target IC50: 0.

4、54 nM (survivin)体外研究 YM155 (30 M) is not sensitive to survivn gene promoter-driven luciferase reporter activity. YM155 showssignificant supression on endogenous survivin expression in PC-3 and PPC-1 human HRPC cells withdeficient p53 via transcriptional inhibition of the survivin gene promoter. YM15

5、5 (100 nM) does not affectprotein expression of c-IAP2, XIAP, Bcl-2, Bcl-xL, Bad, -actin, and -tubulin. YM155 potently inhibits humancancer cell lines (mutated or truncated p53) such as PC-3, PPC-1, DU145, TSU-Pr1, 22Rv1, SK-MEL-5 andA375 with IC50s ranging from 2.3 to 11 nM, respectively 1. YM155 r

6、esultin in an increase in sensitivity ofNSCLC cells to -radiation. YM155 combined with -radiation increases both the number of apoptotic cells andthe activity of caspase-3. In addition, YM155 delays the repair of radiation-induced double-strand breaks innuclear DNA 2.体内研究 YM155 (3 and 10 mg/kg) inhi

7、bits the tumor growth in PC-3 xenografts, without obvious body weight loss andblood cell count decrease. YM155 is highly distributed to tumor tissue in vivo. YM155 shows 80% TGI at adose of 5 mg/kg in PC-3 orthotopic xenografts 1. YM155 in combination with -radiation shows potentantitumor activity a

8、gainst H460 or Calu6 xenografts in nude mice 2. In this orthotopic renal and metastaticlung tumors models, YM155 and IL-2 additively decreases tumor weight, lung metastasis, and luciferin-stainedtumor images 3.PROTOCOLKinase Assay 1 A 2,767-bp sequence of human survivin gene promoter is isolated fro

9、m human genomic DNA by PCR usingPyrobest polymerase and the following primers: 5-GCGCGCTCGAGTCTAGACATGCGGATATATTC-3 and5-GCGCGAA-GCTTTGGCGGTTAATGGCGCGC-3. The resulting PCR fragment is digested withXhoI/HindIII and ligated into the XhoI/HindIII cleavage site of the pGL3-Basic vector. The resulting p

10、lasmid isnamed pSUR-luc. DNA sequencing is done on all amplified sequences by a DNA sequencer. The activity ofpSUR-luc is confirmed by luciferase assay with transiently transfected HeLa-S3 cells. Luciferase assay isdone. The pGL3 control vector, which contains the SV40 promoter and enhancer sequence

11、s, is used. HeLacells are stably transfected with pSUR-luc and pSV2bsr by Lipofect-AMINE 2000. After blasticidin selection at10 g/mL, a single colony is chosen based on appropriate luciferase signals and genetic stability over timeand named HeLa-SURP-luc. CHO cells are stably transfected with pGL3-c

12、ontrol and pSV2bsr. Afterblasticidin selection at 10 g/mL, a single colony is chosen based on appropriate luciferase signals andgenetic stability over time and named CHO-SV40-luc. Stocked cells from the HeLa-SURP-luc and CHO-SV40-luc clones are used for chemical screening and characterization of YM1

13、55. YM155 in DMSO areadded to the cells, which had been seeded the previous day on 96-well plastic plates at 5103 per well.Luciferase activity is measured 24 hours later. IC50 is calculated by logistic analysis.MCE has not independently confirmed the accuracy of these methods. They are for reference

14、 only.Cell Assay 1 The antiproliferative activity of YM-155 is measured. After treatment with YM-155 for 48 h, the cell count isdetermined by sulforhodamine B assay. The GI50 value is calculated by logistic analysis, which is the drugconcentration resulting in a 50% reduction in the net protein incr

15、ease (as measured by sulforhodamine B2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEstaining) in control cells during the drug incubation. The assay is done in triplicate, and the mean GI50 valueis obtained from the results of four independent assays.MCE has not independently confirmed the accurac

16、y of these methods. They are for reference only.Animal Five-week-old male nude mice (BALB/c nu/nu) are used for the assay. PC-3 cells (2106-3106) are injectedAdministration 1 into the flanks of the mice and allowed to reach a tumor volume of 100 mm3 in tumor volume(lengthwidth20.5). YM-155 is s.c. a

17、dministered as a 3-day continuous infusion per week for 2 weeks usingan implanted micro-osmotic pump or i.v. administered five times a week for 2 weeks. The percentage oftumor growth inhibition 14 days after initial YM-155 administration is calculated for each group using thefollowing formula: MTV=1

18、001-(MTV of the treated group on day 14)-(MTV of the treated group on day0)/(MTV of the control group on day 14)-(MTV of the control group on day 0), where MTV is mean tumorvolume. For both the frozen tumors and plasma samples, survivin expression levels are analyzed by Westernblotting and YM-155 dr

19、ug concentration by high-performance liquid chromatography/triple quadrupole massspectrometry (LC/MS/MS) using validated methods.MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cancer Lett. 2018 Jul 1;425:54-64. Cancers (Basel). 2019 Jul 5;11(7). pii: E947. Nutrients. 2018 Mar 15;10(3). pii: E353. Sci Rep. 2019 Aug 21;9(1):12149. Anticancer Res. 2019 Sep;39(9):4817-4828.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Nakahara T, et al. YM155, a novel small-molecule survivin suppressant, induces regression of established hu