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1236699-92-5 分子结构
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N-[(2S)-2,3-dihydroxypropyl]-3-[(2-fluoro-4-iodophenyl)amino]pyridine-4-carboxamide

ChemBase编号:72699
分子式:C15H15FIN3O3
平均质量:431.2007732
单一同位素质量:431.01421758
SMILES和InChIs

SMILES:
c1c(ccc(c1F)Nc1cnccc1C(=O)NC[C@@H](CO)O)I
Canonical SMILES:
OC[C@H](CNC(=O)c1ccncc1Nc1ccc(cc1F)I)O
InChI:
InChI=1S/C15H15FIN3O3/c16-12-5-9(17)1-2-13(12)20-14-7-18-4-3-11(14)15(23)19-6-10(22)8-21/h1-5,7,10,20-22H,6,8H2,(H,19,23)/t10-/m0/s1
InChIKey:
VIUAUNHCRHHYNE-JTQLQIEISA-N

引用这个纪录

CBID:72699 http://www.chembase.cn/molecule-72699.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-[(2S)-2,3-dihydroxypropyl]-3-[(2-fluoro-4-iodophenyl)amino]pyridine-4-carboxamide
IUPAC传统名
N-[(2S)-2,3-dihydroxypropyl]-3-[(2-fluoro-4-iodophenyl)amino]pyridine-4-carboxamide
别名
AS-703026
MSC1936369B
AS703026
N-[(2S)-2,3-Dihydroxypropyl]-3-[(2-fluoro-4-iodophenyl)amino]-4-pyridinecarboxamide
AS-703026
CAS号
1236699-92-5
PubChem SID
162037620
PubChem CID
44187362

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
PubChem 44187362 external link

理论计算性质

理论计算性质

JChem
Acid pKa 13.665774  质子受体
质子供体 LogD (pH = 5.5) 2.3146443 
LogD (pH = 7.4) 2.3209436  Log P 2.321025 
摩尔折射率 92.1961 cm3 极化性 34.815342 Å3
极化表面积 94.48 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)
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成盐信息
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质检报告
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详细说明

详细说明

Selleck Chemicals Selleck Chemicals TRC TRC
Selleck Chemicals -  S1475 external link
Research Area
Description Cancer
Biological Activity
Description AS703026 is a highly selective and potent non-competitive inhibitor of MEK1/2 with IC50 of 5-11 nM.
Targets MEK1/2
IC50 5-11 nM [1]
In Vitro AS703026 is a novel, selective, orally bioavailable MEK1/2 inhibitor that binds to the distinctive MEK allosteric site and therefore exhibits exquisite kinase selectivity. AS703026 inhibits growth and survival of human multiple myeloma (MM) cells, including U266 and INA-6, with IC50 of 5 nM and 11 nM, respectively. Such an inhibitory effect by AS703026 is mediated by G0-G1 cell cycle arrest and is accompanied by reduced expresson of the MAF oncogene. AS703026 further induces apoptosis via caspase-3 and PARP cleavage in MM cells, both in the presence or absence of bone marrow stromal cells (BMSCs). [1]AS703026 may be an effective therapy in colorectal cancer caused by K-Ras mutation. AS703026 (10 μM) effectively inhibits the ERK pathway, proliferation, and transformation in human DLD-1 colorectal cancer cells what carry a mutant allele of K-Ras (D-MUT). [2]
In Vivo AS703026 (15 and 30 mg/kg) significantly inhibits tumor growth in a human plasmacytoma xenograft model of H929 MM cells. This can be correlated with downregulated pERK1/2, induced PARP cleavage, and decreased microvessels. [1]AS703026 (10 mg/kg) inhibits tumor growth, and markedly decreases p-ERK level in a xenograft mouse model of human K-Ras mutated (D-MUT) colorectal tumor. [2]
Clinical Trials AS703026 is currently under Phase II clinical trial for acute myeloid leukemia.
Features AS703026 is a novel, highly selective and potent allosteric inhibitor of MEK1/2.
Protocol
Kinase Assay [3]
MEK1 enzyme assays AS703026 is dissolved in 2.5% DMSO. Activated diphosphorylated MEK (pp-MEK) assays contained 40 μM 33P-γATP (AppKm 8.5 μM), 0.5 nM human-activated MEK1 or MEK2, 1 μM kinase-dead ERK2 (AppKm 0.73 μM). All assays are done in buffer containing 20 mM HEPES (pH 7.2), 5 mM 2-mercaptoethanol, 0.15 mg/mL BSA, and 10 mM MgCl2. The final concentration of 33P- ATP is 0.02 μCi/μL for all the assays. pp-MEK kinase reactions are stopped after 40 min by transferring 30 μL of reaction mixture to Durapore 0.45-μm filters plates containing 12.5% TCA. Filters are dried and read with liquid scintilant on a TopCount. Concentration response data are analyzed for IC50. 0.2 nM recombinant human MEK1 or MEK2 is preincubated with vehicle or with AS703026 for 40 minutes in reaction buffer to determine IC50 of initially unphosphorylated MEK (u-MEK). Phosphorylation/activation is initiated by the addition of a final concentration of 20 nM final B-RafV600E and 30 μM final ATP for 10 min. B-Raf activity is then quenched by addition of the B-Raf inhibitor SB590885 (final concentration 100 nM), and MEK kinase activity is assayed by the addition of 1 μM KD-ERK2 and 0.02 μCi/μL 33P-ATP in reaction buffer. The kinase reactions are stopped after 90 min by transferring 30μL of reaction mixture to a Durapore filter plate, and read as above.
Cell Assay [1]
Cell Lines U266 and INA-6 cells
Concentrations 2 nM - 20 μM (stock: 10 mM in DMSO)
Incubation Time 48 hours
Methods Cytotoxicity assays for AS703026 are assessed by measuring both [3H]thymidine incorporation and MTT dye absorbance. Cells (1 × 104 per well) are cultured in 96-well plates for 3 days. For the [3H]thymidine incorporation assay, cells are pulsed with 18.5 kBq/well [3H]thymidine for 6 hours, harvested onto glass fibre filters, and counted in a β-scintillation counter.Cell cycle analysis is assessed by propidium iodide (PI) staining using flow cytometry. AS703026-induced apoptosis is determined by annexin-V/PI staining and flow cytometric data analysis.
Animal Study [1]
Animal Models H929 MM xenografts are established in CB17 (SCID) mice
Formulation 10 mg/mL, dissolved in 0.5% carboxymethylcellulose / 0.25% Tween20
Doses 15 or 30 mg/kg
Administration Oral gavage twice daily
References
[1] Kim K, et al. Br J Haematol, 2010, 149(4), 537-549.
[2] Yoon J, et al. Cancer Res, 2011, 71(2), 445-453
[3] Gilmartin AG, Clin Cancer Res, 2011, 17(5), 989-1000.
Toronto Research Chemicals -  A780100 external link
AS703026 is a novel, selective, orally bioavailable MEK1/2 inhibitor, in human multiple myeloma (MM). AS703026 induces pleiotropic anti-myeloma activity in vitro and in vivo. MEK inhibitors are useful in the treatment of hyperproliferative diseases, such

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