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
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)
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 |
|---|---|---|---|
Target ID: O14965 Gene ID: 6790.0 Gene Symbol: AURKA Target Organism: Homo sapiens (Human) |
110.0 nM [IC50] | ||
Target ID: Q96GD4|||O60446 Gene ID: 9212.0 Gene Symbol: AURKB Target Organism: Homo sapiens (Human) |
130.0 nM [IC50] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | Unknown Approved UseUnknown |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Phosphorylation of histone H3 serine 10 in early mouse embryos: active phosphorylation at late S phase and differential effects of ZM447439 on first two embryonic mitoses. | 2010-12-01 |
|
| Antiproliferative effect of Aurora kinase targeting in mesothelioma. | 2010-12 |
|
| The Aurora kinase inhibitor ZM447439 accelerates first meiosis in mouse oocytes by overriding the spindle assembly checkpoint. | 2010-10 |
|
| Aurora kinase inhibitor ZM447439 induces apoptosis via mitochondrial pathways. | 2010-01-15 |
|
| 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 |
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| Trivalent dimethylarsenic compound induces histone H3 phosphorylation and abnormal localization of Aurora B kinase in HepG2 cells. | 2009-12-15 |
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| Aurora kinase B modulates chromosome alignment in mouse oocytes. | 2009-11 |
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| Aurora kinase B, epigenetic state of centromeric heterochromatin and chiasma resolution in oocytes. | 2009-09 |
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| Determinants for the efficiency of anticancer drugs targeting either Aurora-A or Aurora-B kinases in human colon carcinoma cells. | 2009-07 |
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| Length of mitotic arrest induced by microtubule-stabilizing drugs determines cell death after mitotic exit. | 2009-06 |
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| Short and long-term tumor cell responses to Aurora kinase inhibitors. | 2009-04-15 |
|
| Investigating the role of Aurora kinases in RAS signaling. | 2009-01-01 |
|
| Cell cycle dependent degradation of MCAK: evidence against a role in anaphase chromosome movement. | 2008-10 |
|
| Regulation of the meiotic prophase I to metaphase I transition in mouse spermatocytes. | 2008-10 |
|
| Molecular basis of drug resistance in aurora kinases. | 2008-06 |
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| Aurora kinase family: a new target for anticancer drug. | 2008-06 |
|
| ZM 447439 inhibition of aurora kinase induces Hep2 cancer cell apoptosis in three-dimensional culture. | 2008-05-15 |
|
| Effects of the aurora kinase inhibitors AZD1152-HQPA and ZM447439 on growth arrest and polyploidy in acute myeloid leukemia cell lines and primary blasts. | 2008-05 |
|
| Requirement of aurora-A kinase in astral microtubule polymerization and spindle microtubule flux. | 2008-04-15 |
|
| A novel treatment strategy targeting Aurora kinases in acute myelogenous leukemia. | 2007-06 |
|
| Inhibition of survivin and aurora B kinase sensitizes mesothelioma cells by enhancing mitotic arrests. | 2007-04-01 |
|
| MAPK interacts with XGef and is required for CPEB activation during meiosis in Xenopus oocytes. | 2007-03-15 |
|
| Caffeine promotes apoptosis in mitotic spindle checkpoint-arrested cells. | 2007-03-09 |
|
| Analysis of mitotic phosphorylation of borealin. | 2007-01-22 |
|
| Inhibition of Aurora kinases perturbs chromosome alignment and spindle checkpoint signaling in rat spermatocytes. | 2006-11-01 |
|
| Frequent overexpression of aurora B kinase, a novel drug target, in non-small cell lung carcinoma patients. | 2006-11 |
|
| Validating Aurora B as an anti-cancer drug target. | 2006-09-01 |
|
| Neither Aurora B activity nor histone H3 phosphorylation is essential for chromosome condensation during meiotic maturation of porcine oocytes. | 2006-05 |
|
| Mitotic requirement for aurora A kinase is bypassed in the absence of aurora B kinase. | 2005-06-20 |
|
| The Ipl1/Aurora kinase family: methods of inhibition and functional analysis in mammalian cells. | 2005 |
|
| Dawn of Aurora kinase inhibitors as anticancer drugs. | 2004-09 |
|
| Aurora B couples chromosome alignment with anaphase by targeting BubR1, Mad2, and Cenp-E to kinetochores. | 2003-04-28 |
Patents
Sample Use Guides
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.
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331771-20-1
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RSN3P9776R
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DTXSID00186833
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9914412
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ZM447439
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91376
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ACTIVE MOIETY
