您当前所在的位置:首页 > 产品中心 > 产品详细信息
718630-59-2 分子结构
点击图片或这里关闭

N-[6,6-dimethyl-5-(1-methylpiperidine-4-carbonyl)-1H,4H,5H,6H-pyrrolo[3,4-c]pyrazol-3-yl]-3-methylbutanamide

ChemBase编号:72709
分子式:C19H31N5O2
平均质量:361.48174
单一同位素质量:361.24777526
SMILES和InChIs

SMILES:
[nH]1nc(c2c1C(N(C2)C(=O)C1CCN(CC1)C)(C)C)NC(=O)CC(C)C
Canonical SMILES:
CC(CC(=O)Nc1n[nH]c2c1CN(C2(C)C)C(=O)C1CCN(CC1)C)C
InChI:
InChI=1S/C19H31N5O2/c1-12(2)10-15(25)20-17-14-11-24(19(3,4)16(14)21-22-17)18(26)13-6-8-23(5)9-7-13/h12-13H,6-11H2,1-5H3,(H2,20,21,22,25)
InChIKey:
HUXYBQXJVXOMKX-UHFFFAOYSA-N

引用这个纪录

CBID:72709 http://www.chembase.cn/molecule-72709.html

Collapse All Expand All

名称和登记号

名称和登记号

名称 登记号
IUPAC标准名
N-[6,6-dimethyl-5-(1-methylpiperidine-4-carbonyl)-1H,4H,5H,6H-pyrrolo[3,4-c]pyrazol-3-yl]-3-methylbutanamide
IUPAC传统名
N-[6,6-dimethyl-5-(1-methylpiperidine-4-carbonyl)-1H,4H-pyrrolo[3,4-c]pyrazol-3-yl]-3-methylbutanamide
别名
PHA-793887
CAS号
718630-59-2
PubChem SID
162037630
PubChem CID
46191454

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
S1487 external link 加入购物车 请登录
数据来源 数据ID
PubChem 46191454 external link

理论计算性质

理论计算性质

JChem
Acid pKa 11.460852  质子受体
质子供体 LogD (pH = 5.5) -1.5170743 
LogD (pH = 7.4) 0.1610957  Log P 1.5650184 
摩尔折射率 104.7277 cm3 极化性 39.081688 Å3
极化表面积 81.33 Å2 可自由旋转的化学键
里宾斯基五规则 true 

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
CDK 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 -  S1487 external link
Research Area
Description Cancer
Biological Activity
Description PHA-793887 is a novel and potent inhibitor of CDK2, CDK5 and CDK7 with IC50 of 8 nM, 5 nM and 10 nM, respectively.
Targets CDK2 CDK5 CDK7
IC50 8 nM 5 nM 10 nM [1]
In Vitro [1]
In Vivo PHA-793887 (10–30 mg/kg) shows good efficacy in the human ovarian A2780, colon HCT-116, and pancreatic BX-PC3 carcinoma xenograft models. [1]PHA-793887 (20 mg/kg) is effective in xenograft models of K562 and HL60 cells, primary leukemic disseminated model, and a high-burden disseminated ALL-2 model derived from a relapsed Philadelphia-positive acute lymphoid leukemia patient. [2]
Clinical Trials A Phase I clinical trial of PHA-793887 for advanced/metastatic solid tumors has been terminated.
Features Multi-CDKs inhibitor.
Protocol
Kinase Assay [3]
CDK Kinase Assay The biochemical activity of compounds is determined by incubation with specific enzymes and substrates, followed by quantitation of the phosphorylated product. PHA-793887 (1.5 nM–10 μM) is incubated for 30?90 min at room temperature in the presence of ATP/33P-γ-ATP mix, substrate, and the specific enzyme (0.7?100 nM) in a final volume of 30 μL of kinase buffer, using 96 U bottom plates. After incubation, the reaction is stopped and the phosphorylated substrate is separated from nonincorporated radioactive ATP using SPA beads, Dowex resin, or Multiscreen phosphocellulose filter as follows: (1) For SPA Assays. The reaction is stopped by the addition of 100 μL of PBS + 32 mM EDTA + 0.1% Triton X-100 + 500 μM ATP, containing 1 mg of streptavidin-coated SPA beads. After 20 min of incubation for substrate capture, 100 μL of the reaction mixture is transferred into Optiplate 96-well plates containing 100 μL of 5 M CsCl, left to stand for 4 hours to allow stratification of beads to the top of the plate, and counted using TopCount to measure substrate-incorporated phosphate. (2) For Dowex Resin Assay. An amount of 150 μL of resin/formate, pH 3.00, is added to stop the reaction and capture unreacted 33P-γ-ATP, separating it from the phosphorylated substrate in solution. After 60 min of rest, 50 μL of supernatant is transferred to Optiplate 96-well plates. After the additon of 150 μL of Microscint 40, the radioactivity is counted in the TopCount. (3) For Multiscreen Assay. The reaction is stopped with the addition of 10 μL of EDTA (150 mM). An amount of 100 μL is transferred to a MultiScreen plate to allow substrate binding to phosphocellulose filter. Plates are then washed three times with 100 μL of H2PO4 (75 mM) filtered by a MultiScreen filtration system, and dried. After the additon of 100 μL of Microscint 0, radioactivity is counted in the TopCount.IC50 values are obtained by nonlinear regression analysis.
Cell Assay [1]
Cell Lines A2780 cells
Concentrations 0.1 nM – 1 μM, dissolved in DMSO
Incubation Time 72 hours
Methods Cells are seeded into 96- or 384-wells plates at final concentration ranging from 1×104 to 3×104 per cm2. After 24 hours, cells are treated using serial dilution of PHA-793887. At 72 hours after the treatment, the amount of cells are evaluated using the CellTiter-Glo assay. IC50 values are calculated using a sygmoidal fitting.
Animal Study [1]
Animal Models Mouse xenograft models of human ovarian A2780, colon HCT-116 and pancreatic BX-PC3 carcinoma
Formulation Dissolved in 5% dextrose solution
Doses 10, 20, and 30 mg/kg
Administration Intravenous injection once daily
References
[1] Brasca MG, et al. Bioorg Med Chem, 2010, 18(5), 1844-1853.
[2] Alzani R, et al. Exp Hematol, 2010, 38(4), 259-269.
[3] Pevarello P, et al. J Med Chem, 2004, 47(13), 3367-3380.

参考文献

参考文献

供应商提供 Google Scholar IconGoogle Scholar PubMed iconPubMed Google Books IconGoogle Books
正在搜索,请耐心等待...(如果遇到网页错误或者长时间没有结果,请刷新页面[F5])

专利

专利

PubChem iconPubChem Patent Google Patent Search IconGoogle Patent

互联网资源

互联网资源

百度图标百度 google iconGoogle