For research use only. Not for therapeutic Use.
NK314 is a novel synthetic benzo[c]phenanthridine alkaloid that shows strong antitumor activity. It inhibited topoisomerase II activity and stabilized topoisomerase II-DNA cleavable complexes. The DNA breaks occurred within 1h after treatment with NK314 even without digestion of topoisomerase II by proteinase K, whereas etoposide required digestion of the enzyme protein in cleavable complex to detect DNA breaks. Pretreatment with topoisomerase II catalytic inhibitors, ICRF-193 and suramin, reduced both cleavable complex-mediated DNA breaks and proteinase K-independent DNA breaks, but protease inhibitors and nuclease inhibitors only decreased the latter.
| Catalog Number | I008311 |
| CAS Number | 208237-49-4 |
| Synonyms | NK314; NK-314; NK 314.;1-hydroxy-2-methoxy-11a,13,14,15-tetrahydro-6aH-[1,3]dioxolo[4/’,5/’:4,5]benzo[1,2-c]pyrrolo[1,2-f]phenanthridin-12-ium chloride |
| Molecular Formula | C22H18ClNO4 |
| Purity | ≥95% |
| Target | topoisomerase II inhibitor |
| Solubility | Soluble in DMSO, not in water |
| Storage | 0 - 4 °C for short term, or -20 °C for long term |
| InChI | InChI=1S/C22H17NO4.ClH/c1-25-17-7-6-13-14-5-4-12-9-18-19(27-11-26-18)10-15(12)21(14)23-8-2-3-16(23)20(13)22(17)24;/h4-7,9-10H,2-3,8,11H2,1H3;1H |
| InChIKey | FXBDAIVJLCTTAW-UHFFFAOYSA-N |
| SMILES | COC1=C(C2=C3CCC[N+]3=C4C(=C2C=C1)C=CC5=CC6=C(C=C54)OCO6)O.[Cl-] |
| Reference | </br>1:DNA-dependent protein kinase and ataxia telangiectasia mutated (ATM) promote cell survival in response to NK314, a topoisomerase IIα inhibitor. Guo L, Liu X, Jiang Y, Nishikawa K, Plunkett W.Mol Pharmacol. 2011 Aug;80(2):321-7. doi: 10.1124/mol.109.057125. Epub 2011 May 5. PMID: 21546556 Free PMC Article</br>2:NK314 potentiates antitumor activity with adult T-cell leukemia-lymphoma cells by inhibition of dual targets on topoisomerase II{alpha} and DNA-dependent protein kinase. Hisatomi T, Sueoka-Aragane N, Sato A, Tomimasu R, Ide M, Kurimasa A, Okamoto K, Kimura S, Sueoka E.Blood. 2011 Mar 31;117(13):3575-84. doi: 10.1182/blood-2010-02-270439. Epub 2011 Jan 18. PMID: 21245486 Free Article</br>3:NK314, a topoisomerase II inhibitor that specifically targets the alpha isoform. Toyoda E, Kagaya S, Cowell IG, Kurosawa A, Kamoshita K, Nishikawa K, Iiizumi S, Koyama H, Austin CA, Adachi N.J Biol Chem. 2008 Aug 29;283(35):23711-20. doi: 10.1074/jbc.M803936200. Epub 2008 Jul 2. PMID: 18596031 Free PMC Article</br>4:NK314, a novel topoisomerase II inhibitor, induces rapid DNA double-strand breaks and exhibits superior antitumor effects against tumors resistant to other topoisomerase II inhibitors. Onda T, Toyoda E, Miyazaki O, Seno C, Kagaya S, Okamoto K, Nishikawa K.Cancer Lett. 2008 Jan 18;259(1):99-110. Epub 2007 Nov 12. PMID: 17998154 </br>5:Inhibition of topoisomerase IIalpha and G2 cell cycle arrest by NK314, a novel benzo[c]phenanthridine currently in clinical trials. Guo L, Liu X, Nishikawa K, Plunkett W.Mol Cancer Ther. 2007 May;6(5):1501-8. PMID: 17513599 Free Article |
