SB590885 化学構造
分子量: 453.54

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Quality Control & MSDS

製品説明

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製品の説明

生物活性

製品説明 SB590885は、0.16nMのKiによる強力なB-Raf阻害剤です。
ターゲット B-Raf
IC50 0.16 nM (Ki) [1]
In vitro試験 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試験 Administration of SB590885 potently decreases tumorigenesis in murine xenografts established from mutant B-Raf-expressing A375P melanoma cells, and modestly inhibits tumor growth. [1]
臨床試験
特集 Displays significant selectivity for B-Raf over c-Raf.

プロトコル (参考用のみ)

細胞アッセイ: [1]

細胞株 Colo205, HT29, A375P, SKMEL28, and MALME-3M
濃度 Dissolved in DMSO, final concentrations ~10 μM
反応時間 72 hours
実験の流れ 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.

動物実験: [1]

動物モデル Female nude mice injected s.c. with of A375P cells
製剤 Dissolved in vehicle [2% N,N-dimethylacetamide, 2% Cremophor EL, and 96% acidified water (pH f4-5)]
投薬量 50 mg/kg/day
投与方法 Injection i.p.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDogMonkeyBaboon
Weight (kg)0.020.151.80.40.0810312
Body Surface Area (m2)0.0070.0250.150.050.020.50.240.6
Km factor361285201220
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

参考

化学情報

Download SB590885 SDF
分子量 453.54
化学式

C27H27N5O2

CAS No. 405554-55-4
保管 2年-20℃
6月-80℃in solvent
別名 N/A
溶解度 (25°C) * In vitro DMSO 5 mg/mL (11.02 mM)
<1 mg/mL (<1 mM)
エタノール <1 mg/mL (<1 mM)
In vivo 2% Cremophor EL, 2% N,N-dimethylacetamide, pH 5.0 30 mg/mL
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
化学名 (E)-5-(2-(4-(2-(dimethylamino)ethoxy)phenyl)-4-(pyridin-4-yl)-1H-imidazol-5-yl)-2,3-dihydroinden-1-one oxime

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Rating
Source Invest New Drugs, 2014, 32(4), 626-35. SB590885 purchased from Selleck
Method Wright’s staining
Cell Lines BCPAP, K1 and 8505C cells
Concentrations 5.2 uM/6.2 uM
Incubation Time 48 h
Results Marked morphological changes were observed for all drug treatments involving SB590885 alone. Cells resulted enriched with massive vacuolization, readily detectable around the nuclei using light microscopy.

文献中の引用 (3)

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description
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