MRK003

MRK003 is a γ-secretase inhibitor exhibits promising in vitro pre-clinical activity in multiple myeloma and non-Hodgkin's lymphoma. MRK003 treatment induced caspase-dependent apoptosis and inhibited proliferation of MM and NHL cell lines and patient cells. Examination of signaling events after treatment showed time-dependent decrease in levels of the notch intracellular domain, Hes1 and c-Myc. MRK003 downregulated cyclin D1, Bcl-Xl and Xiap levels in NHL cells and p21, Bcl-2 and Bcl-Xl in MM cells. In addition, MRK003 caused an upregulation of pAkt, indicating crosstalk with the PI3K/Akt pathway.

中文名称：

(3'R,6S,9R)-5'-(2,2,2-三氟乙基)-2-((E)-3-(4-(三氟甲基)-1-哌啶基)-1-丙烯-1-基)-5,6,7,8,9,10-六氢螺[6,9-亚甲基苯并环辛烯-11,3'-[1,2,5]噻二唑烷] 1',1'-二氧化物

物化属性:

密度：1.41

PSA：61.03000

LOGP：5.83540

1: Tanaka S, Nakada M, Yamada D, Nakano I, Todo T, Ino Y, Hoshii T, Tadokoro Y, Ohta K, Ali MA, Hayashi Y, Hamada J, Hirao A. Strong therapeutic potential of γ-secretase inhibitor MRK003 for CD44-high and CD133-low glioblastoma initiating cells. J Neurooncol. 2015 Jan;121(2):239-50. doi: 10.1007/s11060-014-1630-z. Epub 2014 Oct 8. PubMed PMID: 25293440.

2: Stoeck A, Lejnine S, Truong A, Pan L, Wang H, Zang C, Yuan J, Ware C, MacLean J, Garrett-Engele PW, Kluk M, Laskey J, Haines BB, Moskaluk C, Zawel L, Fawell S, Gilliland G, Zhang T, Kremer BE, Knoechel B, Bernstein BE, Pear WS, Liu XS, Aster JC, Sathyanarayanan S. Discovery of biomarkers predictive of GSI response in triple-negative breast cancer and adenoid cystic carcinoma. Cancer Discov. 2014 Oct;4(10):1154-67. doi: 10.1158/2159-8290.CD-13-0830. Epub 2014 Aug 7. PubMed PMID: 25104330; PubMed Central PMCID: PMC4184927.