| 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)
| Molecular Formula | C29H31N5O4 |
| Molecular Weight | 513.5875 |
| Charge | 0 |
| Count |
MOL RATIO
1 MOL RATIO (average) |
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
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
PubMed
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.
