CAS 173529-46-9|IVX-214|N-(4-methoxybenzenesulfonyl)-N-{2-[(E)-2-(1-oxo-1$l^{5}-pyridin-4-yl)ethenyl]phenyl}acetamide|N-(4-methoxybenzenesulfonyl)-N-{2-[(E)-2-(1-oxo-1$l^{5}-pyridin-4-yl)ethenyl]phe...

General Information

Structure

Molecular Formula

C₂₂H₂₀N₂O₅S

Molecular Mass

424.4696

Exact Mass

424.10929275

Charge

InChI

InChI=1S/C22H20N2O5S/c1-17(25)24(30(27,28)21-11-9-20(29-2)10-12-21)22-6-4-3-5-19(22)8-7-18-13-15-23(26)16-14-18/h3-16H,1-2H3/b8-7+

InChIKey

OCKHRKSTDPOHEN-BQYQJAHWSA-N

Canonic Smiles

COc1ccc(cc1)S(=O)(=O)N(c1ccccc1/C=C/c1cc[n+](cc1)[O-])C(=O)C

Isomeric Smiles

c1cccc(c1N(S(=O)(=O)c1ccc(cc1)OC)C(=O)C)/C=C/c1cc[n+](cc1)[O-]

Calculated Properties

JChem

H Acceptors

H Donor

LogD (pH = 5.5)

2.153845

LogD (pH = 7.4)

2.1538596

Log P

2.1538599

Molar Refractivity

115.9067

Polarizability

44.205864

Polar Surface Area

89.14

Rotatable Bonds

Lipinski's Rule of Five

true

Data Source

Commercial Catalog

Academic Data

Data Source

Names and Identifiers

Synonyms

IVX-214HMN-214

IUPAC Traditional name

N-(4-methoxybenzenesulfonyl)-N-{2-[(E)-2-(1-oxo-1$l^{5}-pyridin-4-yl)ethenyl]phenyl}acetamide

IUPAC name

N-(4-methoxybenzenesulfonyl)-N-{2-[(E)-2-(1-oxo-1$l^{5}-pyridin-4-yl)ethenyl]phenyl}acetamide

Names and Identifiers

Registration numbers

PubChem CID

9888590

PubChem SID

162037628

CAS Number

173529-46-9

Registration numbers

Properties

Physical Property

Solubility

DMSO

Pharmacology Properties

Target

PLK

Product Information

Salt Data

Free Base

Safety Information

Storage Condition

-20°C

Properties

Related Proteins

No Data Available

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Molecular Spectra

No Data Available

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Molecule Details

Selleck Chemicals

S1485

Research Area

Description

Cancer

Biological Activity

Description

HMN-214 (IVX-214) is a potent inhibitor of Polo-like kinase (Plk)1 with IC50 of 118 nM.

Targets

Polo-like kinase (Plk)1

IC₅₀

118 nM ^[1]

In Vitro

HMN-214 is an oral prodrug that is rapidly converted to HMN-176. The in vitro data of HMN-214 are scarce. However, HMN-176, active metabolite of HMN-214, shows potent and broad-spectrumanti-tumor activity against various cancer cells, including HeLa, PC-3, DU-145, MIAPaCa-2, U937, MCF-7, A549, and WiDr, with a mean IC50 value of 118 nM. HMN-176 is also cytotoxic to drug-resistant human and murine cell lines, including P388/CDDP, P388/VCR, K2/CDDP, and K2/VP-16, with IC50 values ranging from 143 nM–265 nM. In HeLa cells, HMN-176 (3 μM) blocks cell cycle at G2/M phase. ^[1]In Doxorubicin-resistant K2/ARS cells, HMN-176 inhibits cell growth with an IC50 value of 2 μM. HMN-176 (3 μM) down-regulates the expression of the multidrug resistance gene (MDR1), due to the disturbance of NF-Y transcription factor binding to the MDR1 promoter. ^[2]In human RPE1 and CFPAC-1 cells, HMN-176 (2.5 μM) delays satisfaction of the spindle assembly checkpoint. HMN-176 (250 nM–2.5 μM) inhibits meiotic spindle assembly and aster formationin Spisula oocytes. HMN-176 (2.5 μM) also inhibits aster microtubule formation from human centrosomes. These results indicate that the anti-tumor activity of HMN-176 is at least partially via disrupting centrosome-mediated MT assembly during mitosis. ^[3]

In Vivo

HMN-214 is an oral pro-drug of HMN-176 with improved oral absorption. HMN-214 (30 mg/kg) triggers no obvious neurotoxicity in mice. In mouse xenograft model of PC-3, A549, and WiDr cells, HMN-214 (10 mg/kg–20 mg/kg) inhibits tumor growth. ^[1]In nude mice model bearing multidrug-resistant KB-A.1 cells, HMN-214 (10 mg/kg–20 mg/kg) significantly suppresses MDR1 mRNA expression. ^[2]

Clinical Trials

Features

Protocol

Kinase Assay ^[]

Cell Assay ^[1]

Cell Lines

HeLa, PC-3, DU-145, MIAPaCa-2, U937, MCF-7, A549, and WiDr cells

Concentrations

0–10 μM, dissolved in DMSO

Incubation Time

72 hours

Methods

Cells are seeded into a 96-well microplate at a density of 3 × 10³–1 × 10⁴ cells/well. Dilutions of HMN-214 or HMN-176 are added the next day and the plate is incubated for 72 hours. The inhibition of growth is measured by the MTT assay and IC50 values are then obtained.