"目录号: HY-14691
MAPK/ERK Pathway-
Refametinib (RDEA119, BAY 86-9766)是口服生物相容性的MEK抑制剂，对MEK1和MEK2的IC50分别为19 nM和47 nM，有抗肿瘤活性。
MEK
相关产品
U0126-PD98059-Trametinib-Selumetinib-PD0325901-Cobimetinib-MEK162-Honokiol-CI-1040-OTS-964-AS703026-GDC-0623-BIX02189-Ro 5126766-TAK-733-
生物活性
Description
Refametinib (RDEA119, BAY 86-9766), is an orally bioavailable selective MEK inhibitor with potential antineoplastic activity (IC50=19 nM MEK1; IC50=47 nM MEK2).IC50 Value: 19 nM (MEK1); 47 nM (MEK2) [1]Target: MEK1; MEK2in vitro: RDEA119 potently inhibited MEK activity in enzyme inhibition assays in a non-ATP-competitive manner (MEK1 IC50 = 19 nmol/L, MEK2 IC50 = 47 nmol/L) determined through incorporation of radioactive phosphate from ATP into ERK as substrate. RDEA119 potently inhibited MEK activity as measured by phosphorylation of ERK1/2 across several human cancer cell lines of different tissue origins and BRAF mutational status with EC50 values ranging from 2.5 to 15.8 nmol/L [1]. BAY 86-9766 exhibited potent antiproliferative activity in HCC cell lines with half-maximal inhibitory concentration values ranging from 33 to 762 nM. BAY 86-9766 was strongly synergistic with sorafenib in suppressing tumor cell proliferation and inhibiting phosphorylation of the extracellular signal-regulated kinase (ERK) [2]. in vivo: RDEA119/BAY 869766 exhibits potent activity in xenograft models of melanoma, colon, and epidermal carcinoma. RDEA119/BAY 869766 exhibits complete suppression of ERK phosphorylation at fully efficacious doses in mice. RDEA119/BAY 869766 shows a tissue selectivity that reduces its potential for central nervous system-related side effects [1]. BAY 86-9766 prolonged survival in Hep3B xenografts, murine Hepa129 allografts, and MH3924A rat allografts. Additionally, tumor growth, ascites formation, and serum alpha-fetoprotein levels were reduced. Synergistic effects in combination with sorafenib were shown in Huh-7, Hep3B xenografts, and MH3924A allografts [2].
Clinical Trial
NCT00785226
Bayer
Advanced Cancer
November 2008
Phase 1-Phase 2
NCT00610194
Bayer
Advanced Cancer
November 2007
Phase 1
NCT02346032
Samsung Medical Center
Biliary Tract Cancer
June 30, 2015
Phase 2
NCT01915589
Bayer
Carcinoma, Hepatocellular
September 16, 2013
Phase 2
NCT01915602
Bayer
Carcinoma, Hepatocellular
September 27, 2013
Phase 2
NCT02168777
Bayer
Neoplasms
June 2014
Phase 1
NCT01392521
Bayer
Neoplasms
July 2011
Phase 1
NCT01764828
Bayer
Neoplasms
February 2013
Phase 1
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References
[1].Iverson C, et al. RDEA119/BAY 869766: a potent, selective, allosteric inhibitor of MEK1/2 for the treatment of cancer. Cancer Res. 2009 Sep 1;69(17):6839-47.
[2].Schmieder R, et al. Allosteric MEK1/2 inhibitor refametinib (BAY 86-9766) in combination with sorafenib exhibits antitumor activity in preclinical murine and rat models of hepatocellular carcinoma. Neoplasia. 2013 Oct;15(10):1161-71.