CAS 848942-61-0|AZD8931|2-[4-({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}oxy)piperidin-1-yl]-N-methylacetamide|2-[4-({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}ox...

General Information

Structure

Molecular Formula

C₂₃H₂₅ClFN₅O₃

Molecular Mass

473.9277032

Exact Mass

473.16299559

Charge

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

Calculated Properties

JChem

Acid pKa

13.53239

H Acceptors

H Donor

LogD (pH = 5.5)

1.2968376

LogD (pH = 7.4)

2.6736393

Log P

2.812373

Molar Refractivity

123.8024

Polarizability

48.292267

Polar Surface Area

88.61

Rotatable Bonds

Lipinski's Rule of Five

true

Data Source

Commercial Catalog

Academic Data

Data Source

Names and Identifiers

Synonyms

AZD8931

IUPAC Traditional name

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

IUPAC name

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

Names and Identifiers

Registration numbers

CAS Number

848942-61-0

PubChem CID

11488320

PubChem SID

162037806

Registration numbers

Properties

Safety Information

Storage Condition

-20°C

Product Information

Salt Data

Free Base

Pharmacology Properties

Target

HER2

EGFR

Properties

Related Proteins

No Data Available

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Molecular Spectra

No Data Available

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Molecule Details

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.