Refametinib

"目录号: HY-14691

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。

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