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940929-33-9 分子结构
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N-(3-aminopropyl)-N-[(1R)-1-(3-benzyl-7-chloro-4-oxo-4H-chromen-2-yl)-2-methylpropyl]-4-methylbenzamide hydrochloride

ChemBase编号:72879
分子式:C31H34Cl2N2O3
平均质量:553.51926
单一同位素质量:552.19464832
SMILES和InChIs

SMILES:
c1cc(ccc1)Cc1c(=O)c2c(oc1[C@H](N(C(=O)c1ccc(cc1)C)CCCN)C(C)C)cc(cc2)Cl.Cl
Canonical SMILES:
NCCCN([C@@H](c1oc2cc(Cl)ccc2c(=O)c1Cc1ccccc1)C(C)C)C(=O)c1ccc(cc1)C.Cl
InChI:
InChI=1S/C31H33ClN2O3.ClH/c1-20(2)28(34(17-7-16-33)31(36)23-12-10-21(3)11-13-23)30-26(18-22-8-5-4-6-9-22)29(35)25-15-14-24(32)19-27(25)37-30;/h4-6,8-15,19-20,28H,7,16-18,33H2,1-3H3;1H/t28-;/m1./s1
InChIKey:
MLMZVWABFOLFGV-LNLSOMNWSA-N

引用这个纪录

CBID:72879 http://www.chembase.cn/molecule-72879.html

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名称和登记号

名称和登记号

名称 登记号
IUPAC标准名
N-(3-aminopropyl)-N-[(1R)-1-(3-benzyl-7-chloro-4-oxo-4H-chromen-2-yl)-2-methylpropyl]-4-methylbenzamide hydrochloride
IUPAC传统名
N-(3-aminopropyl)-N-[(1R)-1-(3-benzyl-7-chloro-4-oxochromen-2-yl)-2-methylpropyl]-4-methylbenzamide hydrochloride
别名
SB 743921
CAS号
940929-33-9
PubChem SID
162037800
PubChem CID
49867937

数据来源

数据来源

所有数据来源 商品来源 非商品来源
数据来源 数据ID 价格
Selleck Chemicals
S2182 external link 加入购物车 请登录
数据来源 数据ID
PubChem 49867937 external link

理论计算性质

理论计算性质

JChem
质子受体 质子供体
LogD (pH = 5.5) 3.2781336  LogD (pH = 7.4) 4.1581855 
Log P 6.272894  摩尔折射率 150.4481 cm3
极化性 57.524975 Å3 极化表面积 72.63 Å2
可自由旋转的化学键 里宾斯基五规则 false 

分子性质

分子性质

安全信息 药理学性质 产品相关信息 生物活性(PubChem)
保存条件
-20°C expand 查看数据来源
作用靶点
Ksp expand 查看数据来源
成盐信息
hydrochloride expand 查看数据来源

详细说明

详细说明

Selleck Chemicals Selleck Chemicals
Selleck Chemicals -  S2182 external link
Research Area
Description Cancer
Biological Activity
Description SB 743921 is a KSP inhibitor with IC50 of 0.2 nM, 0.07 nM, 1.7 nM, 0.06 nM and 14.4 nM in SKOV3, Colo205, MV522, MX1 and P388 cell lines, respectively.
Targets KSP (SKOV3 cells) KSP (Colo205 cells) KSP (MV522 cells) KSP (MX1 cells) KSP (P388 cells)
IC50 0.2 nM 0.07 nM 1.7 nM 0.06 nM 14.4 nM [1]
In Vitro The Ki of SB 743921 for human and mouse KSP is 0.1 nM and 0.12 nM, respectively, while the Ki of SB 743921 for other kinesins including MKLP1, Kin2 is more than 70 μM. SB 743921 blocks assembly of a functional mitotic spindle, thereby causing cell cycle arrest in mitosis and subsequent cell death. SB-743921 has improved potency over ispinesib in both biochemical and cellular assays. [1]
In Vivo SB-743921 is greater efficacy in vivo against P388 leukemia. SB-743921 has significant efficacy in a broad spectrum of tumor models differing from that of taxanes. SB-743921 is shown to have activity against advanced human tumor xenografts Colo205 (complete regressions), MCF-7, SK-MES, H69, OVCAR-3 (complete and partial regressions), and HT-29, MX-1, MDA-MB-231, A2780 (tumor growth delay). SB-743921 doesn’t cause the neuropathy often associated with the tubulin agents. [1]
Clinical Trials SB-743921 has entered in a Phase I clinical trial in the treatment of cancer.
Features
Protocol
Kinase Assay [2]
Biochemistry assay The motor domains of KSP (amino acids 1–360) is expressed as in Escherichia coli BL21(DE3) as COOH-terminal 6-his fusion proteins. Bacterial pellets are lysed in a microfluidizer with a lysis buffer [50 mM Tris-HCl; 50 mM KCl, 10 mM imidazole, 2 mM MgCl2, 8 mM β-mercaptoethanol, 0.1 mM ATP (pH 7.4)], and proteins are purified using Ni-NTA agarose affinity chromatography, with an elution buffer consisting of 50 mM PIPES, 10% sucrose, 300 mM imidazole, 50 mM KCl, 2 mM MgCl2, mM β-mercaptoethanol, and 0.1 mM ATP (pH 6.8). Steady-state measurements of ATPase activity are performed with a pyruvate kinase–lactate dehydrogenase detection system that coupled the appearance of ADP with oxidation of NADH. Absorbance changes are monitored at 340 nm. All biochemical experiments are performed in PEM25 buffer [25 mM Pipes/KOH (pH 6.8), 2 mM MgCl2, 1 mM EGTA] supplemented with 10 μM SB 743921 for experiments involving microtubules. Rates of ADP release are measured in a stopped-flow apparatus; the decrease in fluorescence of MANT-ATP is monitored. Rates of Pi release are measured in a stopped-flow apparatus, using bacterial phosphate binding protein modified with 7-diethylamino-3-((((2 maleimidyl)ethyl)amino)carbonyl)coumarin (MDCC) dye. Ki estimates of KSP inhibitors are extracted from the dose–response curves, with explicit correction for enzyme concentration. Tubulin polymerization by measuring changes in absorbance at 340 nm is monitored. The assay is performed in 100-μL volumes in 96-well half-area microtiter plates, using a microplate reader with the incubation temperature set at 37 °C.
Cell Assay [2]
Cell Lines HeLa cells
Concentrations ~1 μM
Incubation Time 24 hours
Methods All cells including HeLa cells are cultured in 10% FCS in RPMI 1640 in 5% CO 2. We assessed 48-hour growth inhibition by serial dilution of SB 743921 relative to DMSO-treated cells in 96-well microtiter plates, using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium. Cell growth is represented as the ratio of absorbance of treated cells to DMSO control, plotted by concentration and fitted to a four-parameter curve. Concentrations at which cellular growth is inhibited by 50% are extrapolated from the curve fit. The DNA content of HeLa cells cultured in the presence or absence of 1 μM SB 743921 for 24 hours is assessed by propidium iodide staining and flow cytometry. Immunofluorescence images are collected of HeLa cells treated for 24 hours with 1 μM SB 743921, fixed with 2% formaldehyde, permeabilized, and stained with DM1-α, anti-γ-tubulin, and 1 μg/mL 4′,6-diamidino-2-phenylindole, and with Alexa 488 secondary goat antirabbit IgG and Rhodamine-X goat antimouse IgG. Images are collected with a DeltaVision Restoration Microscopy System at a magnification of ×600. Z stacks (0.2 μm) are collected, and out of focus information is removed by constrained iterative deconvolution. Z stacks are then compressed into to a single image plane.
Animal Study [1]
Animal Models Female BDF1 mice with P388 lymphocytic leukemia cells
Formulation 2% dimethylacetamide + 2% Cremophor EL + 96% acidified water [pH 5.0]
Doses 7.5 mg/kg- 30 mg/kg
Administration Administered via i.p.
References
[1] Jackson JR, et al. AACR, 2006, Abst 0906.
[2] Sakowicz R, et al. Cancer Res, 2004, 64(9), 3276-3280.

参考文献

参考文献

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专利

专利

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