ZM-447439

Details

Stereochemistry	ACHIRAL
Molecular Formula	C29H31N5O4
Molecular Weight	513.5875
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=CC2=C(NC3=CC=C(NC(=O)C4=CC=CC=C4)C=C3)N=CN=C2C=C1OCCCN5CCOCC5

InChI

InChIKey=OGNYUTNQZVRGMN-UHFFFAOYSA-N

InChI=1S/C29H31N5O4/c1-36-26-18-24-25(19-27(26)38-15-5-12-34-13-16-37-17-14-34)30-20-31-28(24)32-22-8-10-23(11-9-22)33-29(35)21-6-3-2-4-7-21/h2-4,6-11,18-20H,5,12-17H2,1H3,(H,33,35)(H,30,31,32)

HIDE SMILES / InChI

Molecular Formula	C29H31N5O4
Molecular Weight	513.5875
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19923785

ZM447439 (ZM) is a potent and selective inhibitor of aurora-A and -B kinase with putative anti-tumoral activity. Inhibitors of aurora kinases were shown to induce apoptosis in vitro and in vivo; in addition, ZM447439 inhibits cell division and displays selective toxicity towards proliferating tumor cells versus non-dividing cells. It was discovered, that this drug could be a promising new therapeutic approach in gastroenteropancreatic neuroendocrine tumors (GEP-NETs), which should be evaluated in further clinical trials.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Aurora kinase A 4 Target ID: O14965 Gene ID: 6790.0 Gene Symbol: AURKA Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/12719470	Inhibitor 8297		110.0 nM [IC50]
Aurora kinase B 3 Target ID: Q96GD4\|\|\|O60446 Gene ID: 9212.0 Gene Symbol: AURKB Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/12719470	Inhibitor 8297		130.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Gastroenteropancreatic neuroendocrine tumors 2 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19923785	Primary		Basic research	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Mitotic requirement for aurora A kinase is bypassed in the absence of aurora B kinase.	2005 Jun 20	15922328
Validating Aurora B as an anti-cancer drug target.	2006 Sep 1	16912073
Inhibition of survivin and aurora B kinase sensitizes mesothelioma cells by enhancing mitotic arrests.	2007 Apr 1	17394948
Analysis of mitotic phosphorylation of borealin.	2007 Jan 22	17241471
A novel treatment strategy targeting Aurora kinases in acute myelogenous leukemia.	2007 Jun	17541033
MAPK interacts with XGef and is required for CPEB activation during meiosis in Xenopus oocytes.	2007 Mar 15	17344432
Molecular basis of drug resistance in aurora kinases.	2008 Jun	18559266
Effects of the aurora kinase inhibitors AZD1152-HQPA and ZM447439 on growth arrest and polyploidy in acute myeloid leukemia cell lines and primary blasts.	2008 May	18367484
Length of mitotic arrest induced by microtubule-stabilizing drugs determines cell death after mitotic exit.	2009 Jun	19509263
ZM447439, a novel promising aurora kinase inhibitor, provokes antiproliferative and proapoptotic effects alone and in combination with bio- and chemotherapeutic agents in gastroenteropancreatic neuroendocrine tumor cell lines.	2010	19923785
The Aurora kinase inhibitor ZM447439 accelerates first meiosis in mouse oocytes by overriding the spindle assembly checkpoint.	2010 Oct	20660090

Patents

Sample Use Guides

In Vivo Use Guide

Unknown

Route of Administration: Unknown

In Vitro Use Guide

ZM447439 dose-dependently inhibited proliferation of all three cell lines (BON, QGP-1 and MIP-101) with IC(50) values in the nanomolar to low micromolar range. Moreover, aurora kinase inhibition by ZM447439 potently induced apoptosis, which was accompanied by DNA fragmentation and caspase 3 and 7 activation. Furthermore, we observed cell cycle arrest at G(0)/G(1) phase as well as a block in G(2)/M transition. In addition, combined treatment with the chemotherapeutic agents streptozocin and cisplatin augmented significantly the antiproliferative effects of those agents.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 10:31:18 GMT 2023` Edited by `admin` on `Sat Dec 16 10:31:18 GMT 2023`
Record UNII	RSN3P9776R
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ZM-447439

Common Name

English

ZM 447439 [WHO-DD]

Common Name

English

ZM447439

Code

English

BENZAMIDE, N-(4-((6-METHOXY-7-(3-(4-MORPHOLINYL)PROPOXY)-4-QUINAZOLINYL)AMINO)PHENYL)-

Systematic Name

English

Code System Code Type Description

CAS

331771-20-1