化合物信息

ID:72885

基本信息

化学结构

分子式

C₂₃H₂₅ClFN₅O₃

分子量

473.9277032

精确质量

473.16299559

电荷

InChI

InChI=1S/C23H25ClFN5O3/c1-26-21(31)12-30-8-6-14(7-9-30)33-20-10-15-18(11-19(20)32-2)27-13-28-23(15)29-17-5-3-4-16(24)22(17)25/h3-5,10-11,13-14H,6-9,12H2,1-2H3,(H,26,31)(H,27,28,29)

InChIKey

DFJSJLGUIXFDJP-UHFFFAOYSA-N

Canonic Smiles

CNC(=O)CN1CCC(CC1)Oc1cc2c(ncnc2cc1OC)Nc1cccc(c1F)Cl

Isomeric Smiles

c1(c(cc2c(c1)c(ncn2)Nc1c(F)c(ccc1)Cl)OC)OC1CCN(CC1)CC(=O)NC

计算属性

JChem

Acid pKa

13.53239

质子受体

质子供体

LogD (pH = 5.5)

1.2968376

LogD (pH = 7.4)

2.6736393

Log P

2.812373

摩尔折射率

123.8024

极化性

48.292267

极化表面积

88.61

可自由旋转的化学键

里宾斯基五规则

true

数据来源

产品目录

学术数据

数据来源

名称和标识

别名

AZD8931

IUPAC传统名

2-[4-({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}oxy)piperidin-1-yl]-N-methylacetamide

IUPAC标准名

2-[4-({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}oxy)piperidin-1-yl]-N-methylacetamide

名称和标识

数据登录号

CAS号

848942-61-0

PubChem CID

11488320

PubChem SID

162037806

数据登录号

化合物性质

安全信息

保存条件

-20°C

产品相关信息

成盐信息

Free Base

药理学性质

作用靶点

EGFR

HER2

化合物性质

分子相关蛋白质

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分子图谱

暂无数据

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描述信息

Selleck Chemicals

S2192

Research Area

Description

Cancer

Biological Activity

Description

AZD8931 is a reversible, ATP competitive inhibitor of EGFR, ErbB2 and ErbB3 with IC50 of 4 nM, 3 nM and 4 nM, respectively.

Targets

EGFR

IC₅₀

4 nM

In Vitro

AZD8931 shows different potency to NSCLC and SCCHN cell lines. AZD8931 has high sensitivity to PC-9 cells (EGFR activating mutation) with GI50 of 0.1 nM and low activity to NCI-1437 cells with GI50 above 10 μM. AZD8931 exhibits more potency against phospho-EGFR, phospho-erbB2 and phospho-erbB3 than either lapatinib or gefitinib in PE/CA-PJ41, PE/CA-PJ49, DOK and FaDu cells. ^[1]

In Vivo

AZD8931 reveals antitumor activity in BT474c, Calu-3, LoVo, FaDu and PC-9 xenografts. AZD8931 could reduce p-Akt, Ki67 expression and p-ERK in BT474c xenografts following acute treatment. AZD8931 also causes induction of the M30 apoptosis marker. Furthermore, AZD8931 shows greater proapoptotic effect compared with gefitinib and lapatinib in LoVo xenografts. ^[1]

Clinical Trials

Currently under Phase I clinical trial in Japanese patients with advanced solid malignancies.

Features

Combination Therapy

Description

Combined with paclitaxel, AZD8931 is currently under Phase I clinical trial in Japanese female patients with advanced breast cancer.

Protocol

Kinase Assay ^[1]

Isolated kinase assays

The intracellular kinase domains of human EGFR and erbB2 are cloned and expressed in the baculovirus/Sf21 system. The inhibitory activity of AZD8931 is determined with ATP at Km concentrations (0.4 mM for erbB2 and 2 mM for EGFR) using the ELISA method.

Cell Assay ^[1]

Cell Lines

Head and neck tumor cell lines (KYSE-30, OE21, PE/CA-PJ15, PE/CA-PJ34 (clone C12), PE/CA-PJ41 (clone D2), PE/CA-PJ49, DOK, Detroit562, RPMI2650, SCC-4, SCC-9, SCC-25, CAL 27, SW579, FaDu, Hs 840.T, KB, KYSE-450, and HEp-2, HN5) and NSCLC cell lines (PC-9, Calu-3, NCI-H2073, NCI-H1623, NCI-H522, NCI-H2085, NCI-H2030, NCI-H1703, NCI-H2291, NCI-H2135, NCI-H1975, NCI-H23, NCI-H1650, NCI-H1437, NCI-H3255, and NCI-H1666)

Concentrations

0.001-10 μM

Incubation Time

96 hours

Methods

To determine the antiproliferative activity against cell lines grown in vitro, AZD8931 is tested in a panel of NSCLC and SCCHN cell lines. Cells are incubated for 96 hours with AZD8931 (0.001-10 μM). Viable cell number is determined by 4 hours of incubation with MTS Colorimetric Assay reagent and absorbance measured at 490 nm on a spectrophotometer.