生物活性

• 靶点	KDM1A Ki:1.7μM

• 描述GSK2879552 is a potent, selective and irreversible LSD1 inhibitor. Inhibition of LSD1 by GSK2879552 increased the sensitivity of proliferation of a number of tumor types indicated that small cell lung carcinoma (SCLC), which was associated with DNA hypomethylation. Oral administration of GSK2879552 at dose of 1.5mg/kg inhibited tumor growth of subcutaneous NCI-H526 and NCI-H1417 xenografts by 57% and 83%. GSK2879552 increased H3K4 methylation selectively at genomic regions bound by LSD, resulting in gene expression changes across SCLC cell lines^[2].
• 作用机制GSK2879552 can covalently bind to and form a complex with FAD and LSD1/CoREST.^[2]

• 动物研究
  剂量	Mice: 1.5 mg/kg[1] (p.o.), 33 mg/kg[1] (i.p.)
  给药途径	p.o., i.p.

• 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
  NCT02177812	Leukaemia, Myelocytic, Acute	Phase 1	Terminated(The risk benefit in... more >> relapsed refractory AML does not favor continuation of the study.) Collapse <<	-	United States, Georgia ... more >> GSK Investigational Site Augusta, Georgia, United States, 30912 United States, New York GSK Investigational Site Bronx, New York, United States, 10461 GSK Investigational Site Bronx, New York, United States, 10467 GSK Investigational Site New York, New York, United States, 10065 United States, Texas GSK Investigational Site Houston, Texas, United States, 77030 Australia, Victoria GSK Investigational Site Melbourne, Victoria, Australia, 3004 Canada, Ontario GSK Investigational Site Toronto, Ontario, Canada, M5G 2M9 GSK Investigational Site Toronto, Ontario, Canada, M5G 2M Collapse <<
  NCT02034123	Carcinoma, Small Cell	Phase 1	Terminated(The risk benefit in... more >> relapsed refractory SCLC does not favor continuation of the study) Collapse <<	-	United States, Missouri ... more >> GSK Investigational Site Saint Louis, Missouri, United States, 63110 United States, Ohio GSK Investigational Site Columbus, Ohio, United States, 43210 United States, Tennessee GSK Investigational Site Nashville, Tennessee, United States, 37203 France GSK Investigational Site Villejuif cedex, France, 94805 Spain GSK Investigational Site Barcelona, Spain, 08035 GSK Investigational Site Madrid, Spain, 28034 GSK Investigational Site Madrid, Spain, 28040 GSK Investigational Site Málaga, Spain, 29010 Collapse <<
  NCT02929498	Myelodysplastic Syndrome	Phase 2	Recruiting	May 15, 2019	United States, Pennsylvania ... more >> GSK Investigational Site Recruiting Philadelphia, Pennsylvania, United States, 19111 Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com    Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com Collapse <<

• 参考文献

• [1] Mohammad HP, Smitheman KN, et al. A DNA Hypomethylation Signature Predicts Antitumor Activity of LSD1 Inhibitors in SCLC. Cancer Cell. 2015 Jul 13;28(1):57-69.

  [2] Mohammad HP, Smitheman KN, Kamat CD, Soong D, Federowicz KE, Van Aller GS, Schneck JL, Carson JD, Liu Y, Butticello M, Bonnette WG, Gorman SA, Degenhardt Y, Bai Y, McCabe MT, Pappalardi MB, Kasparec J, Tian X, McNulty KC, Rouse M, McDevitt P, Ho T, Crouthamel M, Hart TK, Concha NO, McHugh CF, Miller WH, Dhanak D, Tummino PJ, Carpenter CL, Johnson NW, Hann CL, Kruger RG. A DNA Hypomethylation Signature Predicts Antitumor Activity of LSD1 Inhibitors in SCLC. Cancer Cell. 2015 Jul 13;28(1):57-69. doi: 10.1016/j.ccell.2015.06.002. PMID: 26175415.