BAY 43-9006: Preclinical data

被引:267
作者
Wilhelm, S [1 ]
Chien, DS [1 ]
机构
[1] Bayer Corp, Div Pharmaceut, Inst Preclin Drug Dev, Bayer Res Ctr, West Haven, CT 06516 USA
关键词
D O I
10.2174/1381612023393026
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The drug design and discovery efforts described in the previous section led to the development of a novel, small molecule Raf-1 kinase inhibitor, BAY 43-9006, which belongs to a class that can be broadly described as bis-aryl ureas (Figure 1) [1]. BAY 43-9006 was identified during a large medicinal chemistry optimization program, and this compound was selected for further pharmacological characterization based on its potent inhibition of Raf-1 (IC50 12 nM) and its favorable kinase selectivity profile [2, 3]. In vitro and in vivo experiments were designed to demonstrate effective blockade of the Raf/MEK/ERK signaling pathway in tumor cells and for anti-tumor efficacy in human xenograft models.
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页码:2255 / 2257
页数:3
相关论文
共 11 条
  • [1] [Anonymous], P AM ASS CANC RES
  • [2] MONOCLONAL-ANTIBODIES DIRECTED TO THE ERBB-2 RECEPTOR INHIBIT IN-VIVO TUMOR-CELL GROWTH
    HARWERTH, IM
    WELS, W
    SCHLEGEL, J
    MULLER, M
    HYNES, NE
    [J]. BRITISH JOURNAL OF CANCER, 1993, 68 (06) : 1140 - 1145
  • [3] Hsieh SS, 2000, INT J CANCER, V86, P644, DOI 10.1002/(SICI)1097-0215(20000601)86:5<644::AID-IJC7>3.0.CO
  • [4] 2-T
  • [5] LYONS JF, 2002, UNPUB PNAS
  • [6] Association of c-Raf expression with survival and its targeting with antisense oligonucleotides in ovarian cancer
    McPhillips, F
    Mullen, P
    Monia, BP
    Dorr, FA
    Smyth, JF
    Langdon, SP
    [J]. BRITISH JOURNAL OF CANCER, 2001, 85 (11) : 1753 - 1758
  • [7] Naumann U, 1997, Recent Results Cancer Res, V143, P237
  • [8] Riedl B., 2001, Proceedings of the American Association for Cancer Research Annual Meeting, V42, P923
  • [9] Blockade of the MAP kinase pathway suppresses growth of colon tumors in vivo
    Sebolt-Leopold, JS
    Dudley, DT
    Herrera, R
    Van Becelaere, K
    Wiland, A
    Gowan, RC
    Tecle, H
    Barrett, SD
    Bridges, A
    Przybranowski, S
    Leopold, WR
    Saltiel, AR
    [J]. NATURE MEDICINE, 1999, 5 (07) : 810 - 816
  • [10] Discovery of heterocyclic ureas as a new class of raf kinase inhibitors: Identification of a second generation lead by a combinatorial chemistry approach
    Smith, RA
    Barbosa, J
    Blum, CL
    Bobko, MA
    Caringal, YV
    Dally, R
    Johnson, JS
    Katz, ME
    Kennure, N
    Kingery-Wood, J
    Lee, W
    Lowinger, TB
    Lyons, J
    Marsh, V
    Rogers, DH
    Swartz, S
    Walling, T
    Wild, H
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2001, 11 (20) : 2775 - 2778