| Field | Specification |
|---|---|
| Target | |
| CAS no. | |
| Applications | |
| Molecular weight | |
| Molecular formula | C30H22N4O2 |
| Purity | |
| SMILES | |
| Form | Solid |
| Storage | |
| Shipping | |
| Catalog no. (Mfr.) | |
| Main SKU |
Compound Overview
ETP-46464 is an effective inhibitor of mTOR and ATR, with IC50 values of 0.6 nM and 14 nM, respectively. It is supplied as a light yellow to yellow solid (C30H22N4O2, MW 470.52) at 99.54% purity.
Physical & Chemical Properties
| CAS Number | 1345675-02-6 |
|---|---|
| Molecular Formula | C30H22N4O2 |
| Molecular Weight | 470.52 g/mol |
| Purity | 99.54% |
| Appearance | Solid |
| Color | Light yellow to yellow |
| SMILES | O=C1N(C2=CC=C(C(C)(C#N)C)C=C2)C3=C4C(C=CC(C5=CN=C(C=CC=C6)C6=C5)=C4)=NC=C3CO1 |
| Target | mTOR, ATR, ATM, DNA-PK, PI3Kα |
| Signaling Pathway | PI3K/Akt/mTOR; Cell Cycle/DNA Damage |
| Solubility | In Vitro: DMSO: 5 mg/mL (10.63 mM; Requires sonication; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO) |
| Storage | Powder: -20°C, 3 years; 4°C, 2 years. In solvent: -80°C, 2 years; -20°C, 1 year. |
| Shipping | Room temperature in continental US; may vary elsewhere. |
Biological Activity
IC50 & Target[1]
|
mTOR 0.6 nM (IC50) |
ATR 14 nM (IC50) |
ATM 545 nM (IC50) |
DNA-PK 36 nM (IC50) |
PI3Kα 170 nM (IC50) |
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 | 5 mg/mL (10.63 mM) | requires sonication; use freshly opened DMSO (absorbed moisture lowers solubility) |
Aliquot the stock solution and store it at -80°C (up to 2 years) or -20°C (up to 1 year); avoid repeated freeze-thaw cycles.
In Vivo
Choose the formulation that suits the animal model and route of administration; percentages are volume ratios of the final working solution. Start from a clear DMSO stock (see In Vitro above), add the co-solvents one at a time in the order listed, mixing after each addition, and prepare the working solution fresh on the day of dosing. If precipitation or phase separation occurs, gentle warming or sonication can help.
Protocol 1
| Composition | 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% saline |
|---|---|
| Result | ≥ 0.5 mg/mL (1.06 mM); clear solution |
| How to prepare | Gives a clear solution at ≥ 0.5 mg/mL (saturation not determined). For 1 mL of working solution: add 100 μL DMSO stock (5.0 mg/mL) to 400 μL PEG300; then 50 μL Tween-80; then 450 μL saline to bring the volume to 1 mL. Saline: dissolve 0.9 g sodium chloride in ddH2O and make up to 100 mL. |
Data provided by the manufacturer.
In Vitro
DNA-PK, PI3Kα and ATM are also inhibited by ETP-46464 (ATRi), with IC50s of 36 nM, 170 nM and 545 nM, respectively[1]. For 72 h, ovarian, endometrial and cervical cancer cell lines, both platinum-sensitive and -resistant, receive varying levels of Cisplatin (0-50 μM), alone or together with ETP-46464 (5.0 μM) and/or KU55933 (10.0 μM). In a subset of cell lines, single-agent dose response analyses show a wide LD50 range for ETP-46464 and KU55933, of 10.0±8.7 and 38.3±7.6 μM respectively. These studies, together with previously published evidence of phospho-Chk1 (Ser345) and phospho-ATM (Ser1981) inhibition after ionizing radiation exposure and dose-response treatments with ETP-46464 and with KU55933, are the basis for choosing the co-treatment doses. In all cell lines tested, ETP-46464 treatment significantly increases the response to Cisplatin, giving 52-89% enhancement in activity, and these effects are synergistic. Combined ATR and ATM inhibition raises the Cisplatin response to a level equal to the one seen with ETP-46464 alone. Independence from p53 status characterizes these effects, which are seen in all gynecologic (GYN) cancer cells tested. ETP-46464 treatment, but not KU55933, sensitizes these GYN cancer cell lines to Cisplatin and also raises the response to Carboplatin[2].
Data provided by the manufacturer. Numbered citations refer to the Literature Cited list in the product description.
Kinase Assay[1]
Deliver compounds (e.g., ETP-46464) and control inhibitors directly to the cell media (100 μL per well) with a multi-well pipette at a final concentration of 10 μM. Homogenize the media by carefully vortexing plates at 500 rpm. Before adding 4-hydroxy-tamoxifen (4-OHT), incubate compounds (e.g., ETP-46464) at 37°C for 15 minutes. Next, to induce ATR activity, add 4-OHT to all wells and incubate for 60 minutes at 37°C. Finally, fix cells with paraformaldehyde and process for IF. Analyze every compound (e.g., ETP-46464) in at least three independent experiments[1].
Cell Assay[2]
Trypsinize cells with 0.25% Trypsin-EDTA, then count them using an automated cell counter and 0.4% Trypan Blue. Seed 96-well plates with KLE, HEC1B and HELA cells at 5000 cells per well, and with OVCAR3, A2780, A2780-CP20 and SIHA cells at 10,000 cells per well. Once cells have attached and reached approximately 60% confluency (24-48 h post seeding), replace the media with fresh media containing Cisplatin (0, 0.78, 1.56, 3.13, 6.25, 12.5, 25 or 50 μM) or, alternatively, Carboplatin (0, 1.56, 3.13, 6.25, 12.5, 25, 50 or 100 μM), each in one of these solutions: 0.15% DMSO; 5 μM ETP-46464; 10 μM KU55933; or 5 μM ETP-46464 together with 10 μM KU55933. Incubate for 72 h. The final concentrations used for ETP-46464 and KU55933 rest on prior evidence of ATR and ATM signaling inhibition, respectively. In a subset of cell lines, single-agent dose response analyses revealed a wide LD50 range for ETP-46464 and KU55933 (10.0±8.7 and 38.3±7.6 μM, respectively). In a similar manner, treat cells with fresh media containing Cisplatin (0, 0.78, 1.56, 3.13, 6.25, 12.5, 25 or 50 μM), supplemented with 0.08% DMSO and 5 μM VE-821. Determine cell viability by the MTS CellTiter 96 Aqueous One Solution Cell Proliferation Assay. Following 2 h of incubation at 37°C, read absorbance at 490 nm with a microplate spectrophotometer. Run each cell line in three biological replicates, and assay every inhibitor(s)/Cisplatin concentration in triplicate within each experiment[2].
Data provided by the manufacturer. Numbered citations refer to the Literature Cited list in the product description.
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CC-223, NSC781406, and BGT226 Exerts a Cytotoxic Effect Against Pancreatic Cancer Cells via mTOR Signaling. Front Pharmacol 2020 Nov 11:11:580407. PMID: 33343350
Combination of PARP inhibitor and temozolomide to suppress chordoma progression. J Mol Med (Berl) 2019 Aug;97(8):1183-1193.
Stage-Specific Regulation of DNA Damage Repair by the Circadian Regulator, CRY1, in Prostate Cancer. bioRxiv 2026 May 21:2026.05.19.726303. PMID: 42239372
