WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H406294
CAS#: 845932-30-1
Description: KU59403 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
Hodoodo Cat#: H406294
Name: KU59403
CAS#: 845932-30-1
Chemical Formula: C29H32N4O4S2
Exact Mass: 564.19
Molecular Weight: 564.720
Elemental Analysis: C, 61.68; H, 5.71; N, 9.92; O, 11.33; S, 11.36
Synonym: KU59403; KU-59403; KU 59403
IUPAC/Chemical Name: 3-(4-methylpiperazin-1-yl)-N-(6-(6-morpholino-4-oxo-4H-pyran-2-yl)thianthren-2-yl)propanamide.
InChi Key: IIBZKDYAYJSSGB-UHFFFAOYSA-N
InChi Code: 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)
SMILES Code: O=C(CCN1CCN(C)CC1)NC2=CC3=C(SC(C(C4=CC(C=C(N5CCOCC5)O4)=O)=CC=C6)=C6S3)C=C2.
Appearance: Off-white to grey solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info:
| Biological target: | KU 59403 is a potent ATM inhibitor, with IC50 values of 3 nM, 9.1 μM and 10 μM for ATM, DNA-PK and PI3K, respectively. |
| In vitro activity: | KU59403 is a novel ATM inhibitor developed from LY294002 (Table 1), which is more potent against ATM than the previous lead KU55933 (IC50 3 nM vs 13 nM), and has at least 1000 times greater specificity for ATM over other members of the PI3K family tested. In contrast to the concentrations of 10 μM of KU55933 and 3 μM KU-600019 needed to induce in vitro chemo- and radio-sensitisation (11, 12), KU59403 was an effective chemo-sensitiser at a concentration of 1 μM. At this concentration KU59403 inhibited ATM activity in SW620 cells by >50%, at the higher concentration of 10 μM KU55933 also substantially inhibited ATM activity (Supplementary figure 3). KU59403 alone was not significantly cytotoxic to LoVo or SW620 cells (88± 7% and 91± 6% survival, respectively) but it enhanced camptothecin cytotoxicity (Figure 1A, Table 2) in both cell lines with greater enhancement being observed in the LoVo compared to the SW620 cells (7-fold; p=0.038 versus 4-fold; p=0.014 at 10 nM camptothecin). KU59403 also significantly enhanced the cytotoxicity of fixed concentrations of etoposide (0.1 and 1 μM) or doxorubicin (10 or 100 nM) in these cell lines, with greater enhancement of etoposide in SW620 cells and of doxorubicin in LoVo cells (Table 2). Reference: Mol Cancer Ther. 2013 Jun;12(6):959-67. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3736091/ |
| In vivo activity: | Tumours in control mice reached 4 times their starting volume (RTV4) at a median time of 6.5 days (Figure 3 A, Table 3). Treatment with etopophos alone caused a modest tumour growth delay of 4 days (time to RTV4 = 10.5 days). This delay was extended to 8.5 days (time to RTV4 = 15 days, p=0.093) when given with KU59403 at 12.5 mg/kg i.p. twice daily for 5 days and 11.5 days (time to RTV4 = 18 days) when given with KU59403 at 25 mg/kg i.p. twice daily for 5 days. This latter treatment was the most effective dosing schedule for KU59403 identified; increasing etopophos efficacy by 190% (p=0.032, Table 3). In contrast, when KU59403 was administered 4 hours after etopophos administration there was no increase in efficacy compared with etopophos alone. In the above studies, neither KU59403 nor etopophos given as a single agent caused any measurable toxicity (maximum body weight loss <2%) and the combination of drugs did not cause unacceptable toxicity (maximum body weight loss = 7%) (Supplementary Figure 5A). Reference: Mol Cancer Ther. 2013 Jun;12(6):959-67. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3736091/ |
The following data is based on the product molecular weight 564.72 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Batey MA, Zhao Y, Kyle S, Richardson C, Slade A, Martin NM, Lau A, Newell DR, Curtin NJ. Preclinical evaluation of a novel ATM inhibitor, KU59403, in vitro and in vivo in p53 functional and dysfunctional models of human cancer. Mol Cancer Ther. 2013 Jun;12(6):959-67. doi: 10.1158/1535-7163.MCT-12-0707. Epub 2013 Mar 19. PMID: 23512991; PMCID: PMC3736091. |
| In vitro protocol: | 1. Batey MA, Zhao Y, Kyle S, Richardson C, Slade A, Martin NM, Lau A, Newell DR, Curtin NJ. Preclinical evaluation of a novel ATM inhibitor, KU59403, in vitro and in vivo in p53 functional and dysfunctional models of human cancer. Mol Cancer Ther. 2013 Jun;12(6):959-67. doi: 10.1158/1535-7163.MCT-12-0707. Epub 2013 Mar 19. PMID: 23512991; PMCID: PMC3736091. |
| In vivo protocol: | 1. Batey MA, Zhao Y, Kyle S, Richardson C, Slade A, Martin NM, Lau A, Newell DR, Curtin NJ. Preclinical evaluation of a novel ATM inhibitor, KU59403, in vitro and in vivo in p53 functional and dysfunctional models of human cancer. Mol Cancer Ther. 2013 Jun;12(6):959-67. doi: 10.1158/1535-7163.MCT-12-0707. Epub 2013 Mar 19. PMID: 23512991; PMCID: PMC3736091. |
1: Batey MA, Zhao Y, Kyle S, Richardson C, Slade A, Martin NM, Lau A, Newell DR, Curtin NJ. Preclinical evaluation of a novel ATM inhibitor, KU59403, in vitro and in vivo in p53 functional and dysfunctional models of human cancer. Mol Cancer Ther. 2013 Jun;12(6):959-67. doi: 10.1158/1535-7163.MCT-12-0707. Epub 2013 Mar 19. PubMed PMID: 23512991; PubMed Central PMCID: PMC3736091.
