生物活性

• 靶点	Survivin IC50:0.54μM

• 描述Survivin is a member of the inhibitor of apoptosis (IAP) protein family and has been implicated in both cell survival and regulation of mitosis in cancer. YM155 is a potent survivin inhibitor with IC₅₀ value of 0.54 nM for survivin promoter activity^[2]. YM155 suppressed expression of survivin and induced apoptosis in PC-3 and PPC-1 human hormone-refractory prostate cancer (HRPC) cell lines at 10 nM, but showed little effect on expression levels of other IAP- or Bcl-2-related proteins up to 100 nM. In a s.c. xenografted PC-3 tumor model in mice, 3-day continuous infusions of YM155 at 3 to 10 mg/kg induced massive tumor regression accompanied by suppression of intratumoral surviving and no significant decreases in body weight were observed^[2]. Glioma cell lines responded in a dose and time-dependent manner to YM-155 with reduction of cell numbers. U373, LN18, LNZ428, T98G, LN229, and LNZ308 cells exhibited an IC₅₀ of ~ 10-75 nM, while A172 cells were resistant to YM-155 with IC₅₀ ~ 250 nM^[3]. Exposure of U373 and LN18 (YM-155 sensitive) glioma cells to 25 nM of YM-155 for 24 h caused a marked loss of mitochondrial membrane potential compared with the control group^[3]. Primary effusion lymphoma-patient-derived xenograft mice were treated with YM-155 (5 mg/kg) from days 2-22. The volume of ascites was significantly less in YM155-treated mice than in control mice on day 22 (0.75 mL [median, range 0-2.56 mL] vs. 3.96 mL [median, range 0.7-5.29 mL], p < 0.01)^[4].
• 细胞研究
• Cell Data

  Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
  A2780cis	0-100 nM	Function Assay	24 h	induces Survivin downregulation	24262875
  A2780cis	5-100 nM	Apoptosis Assay	24/48 h	increases apoptosis in a concentration-dependent manner	24262875
  A2780p	0-100 nM	Function Assay	24 h	induces Survivin downregulation	24262875

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• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT00328588	Lung Cancer C... more >>ancer of Lung Cancer of the Lung Non-Small Cell Lung Carcinoma Carcinoma, Non-Small Cell Lung Collapse <<	Phase 2	Completed	-	Czech Republic ... more >> Chomutov, Czech Republic, 43012 Novi Jicin, Czech Republic, 74101 Ostrava, Czech Republic, 70852 Praha, Czech Republic, 15006 Praha, Czech Republic, 18081 Germany Grosshansdorf, Germany, 22927 Netherlands Amsterdam, Netherlands, 1081HV Amsterdam, Netherlands, 3075 EA Collapse <<
  NCT00257478	Prostate Cancer ... more >> Cancer of Prostate Prostatic Cancer Cancer of the Prostate Collapse <<	Phase 2	Completed	-	United States, Arizona ... more >> Tuscon, Arizona, United States, 85724 United States, California Los Angeles, California, United States, 90033 United States, Idaho Coeur d'Alene, Idaho, United States, 83814 United States, New York Bronx, New York, United States, 10461 New York, New York, United States, 10016 United States, Pennsylvania Philadelphia, Pennsylvania, United States, 19111 United States, Texas San Antonio, Texas, United States, 78229 Netherlands Amsterdam, Netherlands United Kingdom Sutton, Surry, United Kingdom, SM2 5Pt Collapse <<
  NCT00281541	Melanoma	Phase 2	Completed	-	United States, Arizona ... more >> Tuscon, Arizona, United States, 85724 United States, Arkansas Little Rock, Arkansas, United States, 72205 United States, Colorado Aurora, Colorado, United States, 80045 United States, District of Columbia Washington, District of Columbia, United States, 20010 United States, Georgia Atlanta, Georgia, United States, 30322 United States, New Jersey Montclair, New Jersey, United States, 07042 United States, North Carolina Winston-Salem, North Carolina, United States, 27157 United States, Pennsylvania Pittsburgh, Pennsylvania, United States, 15213 United States, Utah Salt Lake City, Utah, United States, 84112 Collapse <<

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• 参考文献

• [2] Nakahara T, Kita A, Yamanaka K, Mori M, Amino N, Takeuchi M, Tominaga F, Hatakeyama S, Kinoyama I, Matsuhisa A, Kudoh M, Sasamata M. YM155, a novel small-molecule survivin suppressant, induces regression of established human hormone-refractory prostate tumor xenografts. Cancer Res. 2007 Sep 1;67(17):8014-21. doi: 10.1158/0008-5472.CAN-07-1343. Erratum in: Cancer Res. 2012 Aug 1;72(15):3886. Mori, Masamichi [added]; Amino, Nobuaki [added]; Hatakeyama, Shinji [added];Minematsu, Tsuyoshi [removed]; Shirasuna, Kenna[removed]. PMID: 17804712.

  [3] Jane EP, Premkumar DR, DiDomenico JD, Hu B, Cheng SY, Pollack IF. YM-155 potentiates the effect of ABT-737 in malignant human glioma cells via survivin and Mcl-1 downregulation in an EGFR-dependent context. Mol Cancer Ther. 2013 Mar;12(3):326-38. doi: 10.1158/1535-7163.MCT-12-0901. Epub 2013 Jan 16. PMID: 23325792; PMCID: PMC3596447.

  [4] Kojima Y, Hayakawa F, Morishita T, Sugimoto K, Minamikawa Y, Iwase M, Yamamoto H, Hirano D, Imoto N, Shimada K, Okada S, Kiyoi H. YM155 induces apoptosis through proteasome-dependent degradation of MCL-1 in primary effusion lymphoma. Pharmacol Res. 2017 Jun;120:242-251. doi: 10.1016/j.phrs.2017.04.006. Epub 2017 Apr 8. PMID: 28396094.