| Field | Specification |
|---|---|
| CAS no. | |
| Applications | |
| Molecular weight | |
| Molecular formula | C26H34N6O2 |
| SMILES | |
| Storage | |
| Shipping | |
| Catalog no. (Mfr.) | |
| Main SKU |
Compound Overview
ATM Inhibitor-8 is a highly potent, selective, orally active ATM inhibitor with an IC50 of 1.15 nM. It exhibits antitumor activity[1]. It has a molecular formula of C26H34N6O2 and a molecular weight of 462.59 g/mol.
Physical & Chemical Properties
| CAS Number | 2956666-60-5 |
|---|---|
| Molecular Formula | C26H34N6O2 |
| Molecular Weight | 462.59 g/mol |
| SMILES | CN(C1=NC2=CC(C3=CN=C(C=C3)OCCCN4CCCCC4)=CC=C2N=C1)C(NC(C)C)=O |
| Signaling Pathway | Cell Cycle/DNA Damage; PI3K/Akt/mTOR |
| Storage | Please store the product under the recommended conditions in the Certificate of Analysis. |
| Shipping | Room temperature in continental US; may vary elsewhere. |
Biological Activity
IC50 & Target
IC50:1.15 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.
[1]. D Deng, et al. Discovery and Evaluation of 3-Quinoxalin Urea Derivatives as Potent, Selective, and Orally Available ATM Inhibitors Combined with Chemotherapy for the Treatment of Cancer via Goal-Oriented Molecule Generation and Virtual Screening. J Med Chem. 2023 Jul 27，
Safety
For Research Use Only. Not for use in diagnostic or therapeutic procedures, and not for human or veterinary use. Handle in accordance with your institution's chemical hygiene plan.
In Vitro
Proliferation of colorectal cancer cells (HCT116, SW620) and breast cancer cells (MCF-7) is inhibited by ATM Inhibitor-8[1]. Combined with 4.22 μM Etoposide and 0.036 μM Irinotecan, ATM Inhibitor-8 (200 nM) inhibits the viability of MCF-7 cells[1]. ATM Inhibitor-8 (200 nM) together with 0.22 μM Irinotecan inhibits the viability of SW620 cells, and it inhibits cell colony formation with 0.02 μM[1].
Western Blot Analysis
| Cell Line | HCT116 cell[1] |
|---|---|
| Concentration | 200 nM |
| Incubation Time | 4 h |
| Result | :Inhibted ATM pathway obviously combined with 25 μM Irinotecan. |
Cell Cycle Analysis
| Cell Line | HCT116 cell[1] |
|---|---|
| Concentration | 200 nM |
| Incubation Time | 48 h |
| Result | Decreased G0/G1 phase cells and increased G0/G1 phase cells with the concentration increase. |
In Vivo
Tumor growth is inhibited when ATM Inhibitor-8 is combined with 40 mg/kg Irinotecan in the SW620 mice model [1]. In Balb/c mice, ATM Inhibitor-8(10 mg/kg, i.v.) has a good PK value, meaning lower plasma clearance, higher plasma exposure, and excellent oral bioavailability. [1].
ATM Inhibitor-8 Pharmacokinetic Analysis in Balb/c Mice[1]
| Route | Dose (mg/kg) | Cmax (ng/mL) | Tmax (h) | t1/2 (h) | Clobs (L·h/kg) | Vss_obs (L/kg) | AUCINF_obs (ng·h/mL) | F (%) |
| i.v. | 10 | 6793.55 | 0.88 | 5.29 | 0.78 | 5.93 | 13027.01 | / |
| p.o. | 10 | 10216.65 | 0.33 | 3.37 | 0.73 | 3.52 | 13952.23 | 107.10 |
| Animal Model | Mouse xenograft model of human colon cancer[1]. |
|---|---|
| Dosage | 40 mg/kg combined with Irinotecan(40 mg/kg) |
| Administration | ATM Inhibitor-8, 20 or 40 mg/kg, p.o. once daily for 3 days every week starting 24 h post-irinotecan dosing (40 mg/kg, i.p. once weekly). |
| Result | Inhibited tumor growth significantly. |
Data provided by the manufacturer. Numbered citations refer to the Literature Cited list in the product description.
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