| Field | Specification |
|---|---|
| CAS no. | |
| Applications | |
| Molecular weight | |
| Molecular formula | C29H32N4O4S2 |
| Purity | |
| SMILES | |
| Form | Solid |
| Storage | |
| Shipping | |
| Catalog no. (Mfr.) | |
| Main SKU |
Compound Overview
KU 59403 is a potent ATM inhibitor, with IC50 values of 3 nM for ATM, 9.1 μM for DNA-PK, and 10 μM for PI3K[1]. It is supplied as a white to yellow solid (C29H32N4O4S2, MW 564.72) at 99.10% purity.
Physical & Chemical Properties
| CAS Number | 845932-30-1 |
|---|---|
| Molecular Formula | C29H32N4O4S2 |
| Molecular Weight | 564.72 g/mol |
| Purity | 99.10% |
| Appearance | Solid |
| Color | White to yellow |
| SMILES | O=C(NC(C=C1S2)=CC=C1SC3=C2C=CC=C3C4=CC(C=C(N5CCOCC5)O4)=O)CCN6CCN(C)CC6 |
| Signaling Pathway | Cell Cycle/DNA Damage; PI3K/Akt/mTOR |
| Solubility | In Vitro: DMSO: 10 mg/mL (17.71 mM; Requires sonication and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO) |
| Storage | -20°C, sealed storage, away from moisture. In solvent: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). |
| Shipping | Room temperature in continental US; may vary elsewhere. |
Biological Activity
IC50 & Target
IC50: 3 nM (ATM)[1].
Literature Cited
Sources cited in this description and in the In Vitro & In Vivo Data tab. Peer-reviewed publications that used this product are listed under References.
Safety
For Research Use Only. Not for use in diagnostic or therapeutic procedures, and not for human or veterinary use. Handle in accordance with the Safety Data Sheet and your institution's chemical hygiene plan.
In Vitro
| Solvent | Solubility | Notes |
|---|---|---|
| DMSO | 10 mg/mL (17.71 mM) | requires sonication and warming and heat to 60°C; use freshly opened DMSO (absorbed moisture lowers solubility) |
Aliquot the stock solution and store it at -80°C (up to 6 months) or -20°C (up to 1 month); sealed storage, away from moisture; avoid repeated freeze-thaw cycles.
Data provided by the manufacturer.
In Vitro
KU 59403 (1 μM) increases VP-16 (1 μM) cytotoxicity to a similar degree in HCT116 and HCT116-N7 cells. In the p53 mutant SW620 cells and the human breast cancer cell line MDAMB-231, sensitization is 11.9±4.7-fold and 3.8±1.8-fold, respectively. KU 59403 (1 μM) inhibits IR-induced ATM activity by approximately 50% in MDA-MB231 cells and by >50% in HCT116 cells, which have low ATM expression and activity[1].
Cell Viability Assay[1]
| Cell Line | LoVo, HCT116 and SW620 (human colon cancer), and U2OS (human osteosarcoma) and MDA-MB-231 (human breast cancer) cells. |
|---|---|
| Concentration | 1 μM. |
| Incubation Time | 16 hours. |
| Result | Had at least 1000 times greater specificity for ATM over other members of the PI3K family tested. Enhanced camptothecin cytotoxicity in both cell lines with greater enhancement being observed in the LoVo compared to the SW620 cells. Significantly enhanced the cytotoxicity of fixed concentrations of VP-16 (0.1 and 1 μM) or NSC 123127 (10 or 100 nM) in these cell lines, with greater enhancement of VP-16 in SW620 cells and of NSC 123127 in LoVo cells. |
In Vivo
A single daily dose of 12.5 mg/kg KU59403 produces significant sensitization[1]. Raising the KU59403 dose to 25 mg/kg given twice daily yields the greatest chemo-sensitization, a 3-fold increase in BMY-40481-induced tumor growth delay in both SW620 and HCT116-N7 xenografts, without significantly increased toxicity[1].
| Animal Model | CD-1 nude mice implanted with SW620 or HCT116-N7 human cancer cell lines at 1×107 cells per animal s.c. (n=5 per group)[1]. |
|---|---|
| Dosage | 6, 12.5 and 25 mg/kg. |
| Administration | I.P. twice daily (0 and 4 hours) and 12.5 mg/kg once daily. |
| Result | Treatment with BMY-40481 alone causes a modest tumour growth delay of 4 days (time to RTV4=10.5 days). This delay is extended to 8.5 days when given with KU 59403 at 12.5 mg/kg i.p. twice daily for 5 days and 11.5 days (time to RTV4=18 days) when given with KU 59403 at 25 mg/kg i.p. twice daily for 5 days. |
Data provided by the manufacturer. Numbered citations refer to the Literature Cited list in the product description.
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LIG1 Loss in TP53-mutant Triple Negative Breast Cancer Rewires DNA Repair and Confers Sensitivity to PARP-ATR Inhibitor Combinations. Mol Cancer Ther 2026 Jul 15:10.1158/1535-7163.MCT-26-0182. PMID: 42456172
Patent. US20250049807A1.
