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398493-79-3 分子结构
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N-(2,6-diethylphenyl)-3-[4-(4-methylpiperazin-1-yl)benzamido]-1H,4H,5H,6H-pyrrolo[3,4-c]pyrazole-5-carboxamide

ChemBase编号:72687
分子式:C28H35N7O2
平均质量:501.6232
单一同位素质量:501.2852234
SMILES和InChIs

SMILES:
c1(ccc(cc1)C(=O)Nc1c2c([nH]n1)CN(C2)C(=O)Nc1c(cccc1CC)CC)N1CCN(CC1)C
Canonical SMILES:
CCc1cccc(c1NC(=O)N1Cc2c(C1)[nH]nc2NC(=O)c1ccc(cc1)N1CCN(CC1)C)CC
InChI:
InChI=1S/C28H35N7O2/c1-4-19-7-6-8-20(5-2)25(19)29-28(37)35-17-23-24(18-35)31-32-26(23)30-27(36)21-9-11-22(12-10-21)34-15-13-33(3)14-16-34/h6-12H,4-5,13-18H2,1-3H3,(H,29,37)(H2,30,31,32,36)
InChIKey:
OBWNXGOQPLDDPS-UHFFFAOYSA-N

引用这个纪录

CBID:72687 http://www.chembase.cn/molecule-72687.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-(2,6-diethylphenyl)-3-[4-(4-methylpiperazin-1-yl)benzamido]-1H,4H,5H,6H-pyrrolo[3,4-c]pyrazole-5-carboxamide
IUPAC传统名
N-(2,6-diethylphenyl)-3-[4-(4-methylpiperazin-1-yl)benzamido]-1H,4H,6H-pyrrolo[3,4-c]pyrazole-5-carboxamide
别名
PHA-680632
CAS号
398493-79-3
PubChem SID
162037608
PubChem CID
11249084

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
S1454 external link 加入购物车 请登录
数据来源 数据ID
PubChem 11249084 external link

理论计算性质

理论计算性质

JChem
Acid pKa 10.493449  质子受体
质子供体 LogD (pH = 5.5) 2.364922 
LogD (pH = 7.4) 4.0801616  Log P 4.5821342 
摩尔折射率 151.7333 cm3 极化性 54.818478 Å3
极化表面积 96.6 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

理化性质 安全信息 药理学性质 产品相关信息 生物活性(PubChem)
溶解度
DMSO expand 查看数据来源
保存条件
-20°C expand 查看数据来源
作用靶点
Aurora Kinase expand 查看数据来源
成盐信息
Free Base expand 查看数据来源

详细说明

详细说明

Selleck Chemicals Selleck Chemicals
Selleck Chemicals -  S1454 external link
Research Area
Description Cancer
Biological Activity
Description PHA-680632 is potent inhibitor of Aurora A, Aurora B and Aurora C with IC50 of 27 nM, 135 nM and 120 nM, repectively.
Targets Aurora A Aurora B Aurora C
IC50 27 nM 135 nM 120 nM [1]
In Vitro PHA-680632 potently inhibits all three Aurora kinases (A, B, and C) with IC50 values of 27, 135, and 120 nM, respectively. PHA-680632 is selective for Aurora kinases, with 10- to 200-fold higher IC50 for FGFR1, FLT3, LCK, PLK1, STLK2, VEGFR2, and VEGFR3, and with IC50 higher than 10 μM for another 22 kinases. PHA-680632 shows potent anti-proliferative effects in a wide range of cell types with IC50 values of 0.06–7.15 μM, including HeLa, HCT116, HT29, LOVO, DU145, and NHDF cells. PHA-680632 (0.5 μM) causes polyploidy in tumor cells. The mechanism of action of PHA-680632 is in agreement with inhibition of Aurora kinases. [1]PHA680632 in association with radiation leads to additive effects in cancer cells, especially in the p53-deficient cells. Combined ionising radiation (IR) and treatment of PHA680632 (100–400 nM) prior to IR leads to an enhancement of radiation-induced Annexin V positive cells, micronuclei formation, and Brca1 foci formation only in HCT116 cells with deficient p53, other than the p53 wild-type counterparts. [2]
In Vivo HA-680632 (15–60 mg/kg) inhibits tumor growth in mice xenografts models of HL60, A2780, and HCT116 cells, by reducing tumor cell proliferation and increasing apoptosis. PHA-680632 (45 mg/kg) suppresses growth of activated ras-driven mammary tumors in mouse mammary tumor virus v-Ha-ras transgenic mice and results in complete tumor stabilization and partial regression. [1]
Clinical Trials
Features
Protocol
Kinase Assay [1]
Aurora Kinase Inhibition Assay Inhibition of kinase activity by PHA-680632 is assessed using a scintillation proximity assay format. The biotinylated substrate is transphosphorylated by the kinase in presence of ATP traced with γ33-ATP. The phosphorylated substrate is then captured using streptavidin-coated scintillation proximity assay beads and the extent of phosphorylation is evaluated by β-counter after a 4-hour rest for the floatation of the beads on a dense 5 M CsCl solution. In particular, a peptide derived from the Chocktide sequence (LRRWSLGL) is used as substrate for Aurora A, whereas the optimized peptide Auroratide is employed for Aurora B and C. The assay is run in a robotized format on 96-well plates. The potency of the compound toward Aurora kinases is evaluated and IC50 values are determined.
Cell Assay [1]
Cell Lines HeLa, HCT116, HT29, LOVO, DU145, and NHDF cells
Concentrations 0.001-1 μM, dissolved in DMSO as 10 mM stock solution
Incubation Time 72 hours
Methods Cells (5×103 to 1.5×104 per cm2) are seeded in 24-well plate. After 24 hours, plates are treated with PHA-680632 and incubated for 72 hours. At the end of incubation time, cells are detached from each plate and counted using a cell counter. IC50s are calculated using percentage of growth versus untreated control.
Animal Study [2]
Animal Models Mice (female athymic nude) xenografts models of p53?/? HCT116 cells
Formulation Dissolved in 20% Tween-80 in 5% glucose solution
Doses 40 mg/kg
Administration Intraperitoneal (i.p.) injection twice a day
References
[1] Soncini C, et al. Clin Cancer Res, 2006, 12(13), 4080-4089.
[2] Tao Y, et al. Br J Cancer, 2007, 97(12), 1664-1672.

参考文献

参考文献

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专利

专利

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