For research use only. Not for therapeutic Use.
KU59403 (Cat No.:I007537) is a potent and selective ATM (Ataxia telangiectasia mutated) inhibitor with with potential anticancer activity. KU59403 was not cytotoxic to human cancer cell lines (SW620, LoVo, HCT116, and MDA-MB-231) per se but significantly increased the cytotoxicity of topoisomerase I and II poisons: camptothecin, etoposide, and doxorubicin. KU59403 significantly enhanced the antitumor activity of topoisomerase poisons in mice bearing human colon cancer xenografts (SW620 and HCT116) at doses that were nontoxic alone and well-tolerated in combination
| Catalog Number | I007537 |
| CAS Number | 845932-30-1 |
| Synonyms | ;3-(4-methylpiperazin-1-yl)-N-(6-(6-morpholino-4-oxo-4H-pyran-2-yl)thianthren-2-yl)propanamide. |
| Molecular Formula | C29H32N4O4S2 |
| Purity | ≥95% |
| Target | ATM inhibitor |
| Solubility | Soluble in DMSO, not in water |
| Storage | 0 - 4°C for short term , or -20°C for long term. |
| IUPAC Name | 3-(4-methylpiperazin-1-yl)-N-[6-(6-morpholin-4-yl-4-oxopyran-2-yl)thianthren-2-yl]propanamide |
| InChI | InChI=1S/C29H32N4O4S2/c1-31-9-11-32(12-10-31)8-7-27(35)30-20-5-6-24-26(17-20)38-25-4-2-3-22(29(25)39-24)23-18-21(34)19-28(37-23)33-13-15-36-16-14-33/h2-6,17-19H,7-16H2,1H3,(H,30,35) |
| InChIKey | IIBZKDYAYJSSGB-UHFFFAOYSA-N |
| SMILES | CN1CCN(CC1)CCC(=O)NC2=CC3=C(C=C2)SC4=C(C=CC=C4S3)C5=CC(=O)C=C(O5)N6CCOCC6 |
| Reference | 1:Mol Cancer Ther. 2013 Jun;12(6):959-67. doi: 10.1158/1535-7163.MCT-12-0707. Epub 2013 Mar 19. Preclinical evaluation of a novel ATM inhibitor, KU59403, in vitro and in vivo in p53 functional and dysfunctional models of human cancer.Batey MA,Zhao Y,Kyle S,Richardson C,Slade A,Martin NM,Lau A,Newell DR,Curtin NJ, PMID: 23512991 PMCID: PMC3736091 DOI: 10.1158/1535-7163.MCT-12-0707 </br><span>Abstract:</span> Ataxia telangiectasia mutated (ATM) kinase signals DNA double-strand breaks (DSB) to cell-cycle arrest via p53 and DNA repair. ATM-defective cells are sensitive to DSB-inducing agents, making ATM an attractive target for anticancer chemo- and radiosensitization. KU59403 is an ATM inhibitor with the potency, selectivity, and solubility for advanced preclinical evaluation. KU59403 was not cytotoxic to human cancer cell lines (SW620, LoVo, HCT116, and MDA-MB-231) per se but significantly increased the cytotoxicity of topoisomerase I and II poisons: camptothecin, etoposide, and doxorubicin. Chemo- and radiosensitization by ATM inhibition was not p53-dependent. Following administration to mice, KU59403 distributed to tissues and concentrations exceeding those required for in vitro activity were maintained for at least 4 hours in tumor xenografts. KU59403 significantly enhanced the antitumor activity of topoisomerase poisons in mice bearing human colon cancer xenografts (SW620 and HCT116) at doses that were nontoxic alone and well-tolerated in combination. Chemosensitization was both dose- and schedule-dependent. KU59403 represents a major advance in ATM inhibitor development, being the first compound to show good tissue distribution and significant chemosensitization in in vivo models of human cancer, without major toxicity. KU59403 provides the first proof-of-principle preclinical data to support the future clinical development of ATM inhibitors.©2013 AACR |
