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SB590885

产品号 S2220 公司名称 Selleck Chemicals
CAS号 405554-55-4 公司网站 http://www.selleckchem.com
分子式 C27H27N5O2 电 话 (877) 796-6397
分子量 453.53558 传 真 (832) 582-8590
纯 度 电子邮件 sales@selleckchem.com
保 存 -20°C Chembase数据库ID: 72908

产品价格信息

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产品别名

标题
SB590885
IUPAC标准名
[2-(4-{5-[(1E)-1-(hydroxyimino)-2,3-dihydro-1H-inden-5-yl]-4-(pyridin-4-yl)-1H-imidazol-2-yl}phenoxy)ethyl]dimethylamine
IUPAC传统名
[2-(4-{4-[(1E)-1-(hydroxyimino)-2,3-dihydroinden-5-yl]-5-(pyridin-4-yl)-3H-imidazol-2-yl}phenoxy)ethyl]dimethylamine
别名
SB 590885

产品登记号

CAS号 405554-55-4

产品性质

作用靶点 B-Raf
成盐信息 Free Base
保存条件 -20°C

产品详细信息

详细说明 (English)
Research Area
Description Cancer
Biological Activity
Description SB590885 is a potent B-Raf inhibitor with Ki of 0.16 nM.
Targets B-Raf
IC50 0.16 nM (Ki) [1]
In Vitro SB590885 displays significant selectivity for B-Raf over c-Raf with Ki of 0.16 nM over 1.72 nM. SB-590885 is a more potent inhibitor than the previously described Raf/VEGFR kinase inhibitor BAY 439006 (Ki = 38 nM for mutant B-Raf, 6 nM for c-Raf). SB590885 displays potent selectivity over 46 other kinases. Unlike the multi-kinase inhibitor BAY43-9006, SB590885 stabilizes the oncogenic B-Raf kinase domain in an active configuration. In Colo205, HT29, A375P, SKMEL28, and MALME-3M cells expressing oncogenic B-RafV600E, SB590885 treatment potently inhibits ERK phosphorylation with EC50 of 28 nM, 58 nM, 290 nM, 58 nM, and 190 nM, respectively, and consistently, inhibits the proliferation with EC50 of 0.1 μM, 0.87 μM, 0.37 μM, 0.12 μM, and 0.15 μM, respectively. SB590885 decreases anchorage-independent growth of melanoma cell lines in a BRAF mutant-selective manner. [1] SB590885 displays high affinity for B-Raf with Kd of 0.3 nM. [2] Most of the melanoma cell lines that harbor the BRAF V600E mutation and lack CDK4 mutations (451Lu, WM35, and WM983) are highly sensitive to SB590885 with IC50 of <1 μm.="" increased="" levels="" of="" cyclin="" d1="" resulting="" from="" genomic="" amplification="" mediate="" sb590885="" resistance="" in="" b-raf="" v600e-mutated="" melanomas.="">[3]
In Vivo Administration of SB590885 potently decreases tumorigenesis in murine xenografts established from mutant B-Raf-expressing A375P melanoma cells, and modestly inhibits tumor growth. [1]
Clinical Trials
Features SB590885 displays significant selectivity for B-Raf over c-Raf.
Protocol
Cell Assay [1]
Cell Lines Colo205, HT29, A375P, SKMEL28, and MALME-3M
Concentrations Dissolved in DMSO, final concentrations ~10 μM
Incubation Time 72 hours
Methods Cells are treated with increasing concentrations of SB590885 and incubated for 72 hours. Viable cells are quantified using CellTiter-Glo reagent and luminescence detection on a Victor 2V plate reader. Cells are prepared for cell cycle analysis on a Becton Dickinson FACScan. Data is acquired and analyzed using CellQuest v3.3 software.
Animal Study [1]
Animal Models Female nude mice injected s.c. with of A375P cells
Formulation Dissolved in vehicle [2% N,N-dimethylacetamide, 2% Cremophor EL, and 96% acidified water (pH f4–5)]
Doses 50 mg/kg/day
Administration Injection i.p.
References
[1] King AJ, et al. Cancer Res, 2006, 66(23), 11100-11105.
[2] Takle AK, et al. Bioorg Med Chem Lett, 2006, 16(2), 378-381.
[3] Smalley KS, et al. Mol Cancer Ther, 2008, 7(9), 2876-2883.