1. PI3K/Akt/mTOR Cell Cycle/DNA Damage
  2. mTOR ATM/ATR
  3. ETP-46464

ETP-46464 is an effective mTOR and ATR inhibitor with IC50s of 0.6 and 14 nM, respectively.

For research use only. We do not sell to patients.

ETP-46464 Chemical Structure

ETP-46464 Chemical Structure

CAS No. : 1345675-02-6

Size Price Stock Quantity
Solid + Solvent
10 mM * 1 mL in DMSO
ready for reconstitution
USD 77 In-stock
Solution
10 mM * 1 mL in DMSO USD 77 In-stock
Solid
5 mg USD 70 In-stock
10 mg USD 110 In-stock
25 mg USD 220 In-stock
50 mg USD 350 In-stock
100 mg USD 560 In-stock
200 mg   Get quote  
500 mg   Get quote  

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Based on 2 publication(s) in Google Scholar

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  • Biological Activity

  • Protocol

  • Purity & Documentation

  • References

  • Customer Review

Description

ETP-46464 is an effective mTOR and ATR inhibitor with IC50s of 0.6 and 14 nM, respectively.

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)

In Vitro

ETP-46464 (ATRi) also inhibits DNA-PK, PI3Kα and ATM with IC50s of 36 nM, 170 nM and 545 nM, respectively[1]. Platinum-sensitive and -resistant ovarian, endometrial and cervical cancer cell lines are treated with varying levels of Cisplatin (0-50 µM) with or without the ETP-46464 (5.0 µM) and/or the KU55933 (10.0 µM) for 72 h. Single-agent dose response analyses of ETP-46464 and KU55933 in a subset of cell lines reveal a wide LD50 range of 10.0±8.7 and 38.3±7.6 µM respectively. Co-treatment doses are chosen based on these studies and previously published evidence of phospho-Chk1 (Ser345) and phospho-ATM (Ser1981) inhibition following ionizing radiation exposure and dose response treatments with ETP-46464 and KU55933. Treatment with ETP-46464 significantly increases the response of Cisplatin in all cell lines tested, resulting in 52-89% enhancement in activity and are synergistic. The combined inhibition of ATR and ATM enhances the response of Cisplatin to a level equivalent to that observed using ETP-46464 alone. These effects are independent of p53 status, and are observed in all gynecologic (GYN) cancer cells tested. Treatment with ETP-46464, but not KU55933, not only sensitizes these GYN cancer cell lines to Cisplatin, but also enhances the response of Carboplatin[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Molecular Weight

470.52

Formula

C30H22N4O2

CAS No.
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

Shipping

Room temperature in continental US; may vary elsewhere.

Storage
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 2 years
-20°C 1 year
Solvent & Solubility
In Vitro: 

DMSO : 5 mg/mL (10.63 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 2.1253 mL 10.6265 mL 21.2531 mL
5 mM 0.4251 mL 2.1253 mL 4.2506 mL
View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

  • Molarity Calculator

  • Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass
=
Concentration
×
Volume
×
Molecular Weight *

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

Concentration (start)

C1

×
Volume (start)

V1

=
Concentration (final)

C2

×
Volume (final)

V2

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

  • Protocol 1

    Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% Saline

    Solubility: ≥ 0.5 mg/mL (1.06 mM); Clear solution

    This protocol yields a clear solution of ≥ 0.5 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (5.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

    Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

g

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO +
+
%
Tween-80 +
%
Saline
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Calculation results:
Working solution concentration: mg/mL
Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
 If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Purity & Documentation

Purity: 99.55%

References
Kinase Assay
[1]

Compounds (e.g., ETP-46464) and control inhibitors are delivered directly to cell media (100 μL per well) with a multi-well pipette at a final concentration of 10 μM. Media content is homogenized by carefully vortexing plates at 500 rpm. Prior to 4-hydroxy-tamoxifen (4-OHT) addition, Compounds (e.g., ETP-46464 ) are incubated at 37ºC for 15 minutes. Next, to induce ATR activity, 4-OHT is added to all wells and incubated for 60 minutes at 37ºC. Finally, cells are fixed with paraformaldehyde and processed for IF. Every compound (e.g., ETP-46464) is analyzed at least in three independent experiments[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Assay
[2]

Cells are trypsinized with 0.25% Trypsin-EDTA and counted with 0.4% Trypan Blue using an automated cell counter and plated in 96-well plates at 5000 cells per well for KLE, HEC1B and HELA and 10,000 cells per well for OVCAR3, A2780, A2780-CP20 and SIHA. After cells attach and reach approximately 60% confluency (24-48 h post seeding), media is removed and replaced with fresh media containing Cisplatin (0, 0.78, 1.56, 3.13, 6.25, 12.5, 25 or 50 µM) or Carboplatin (0, 1.56, 3.13, 6.25, 12.5, 25, 50 or 100 µM) in 0.15% DMSO, 5 µM ETP-46464, 10 µM KU55933, or a combination of 5 µM ETP-46464 and 10 µM KU55933 and incubated for 72 h. Final concentrations of ETP-46464 and KU55933 utilized are based on prior evidence indicating inhibition of ATR and ATM signaling, respectively. Single-agent dose response analyses of ETP-46464 and KU55933 in a subset of cell lines revealed a wide LD50 range (10.0±8.7 and 38.3±7.6 µM, respectively). Similarly, cells are treated with fresh media containing Cisplatin (0, 0.78, 1.56, 3.13, 6.25, 12.5, 25 or 50 µM) in 0.08% DMSO and 5 µM VE-821. Cell viability is assessed using the MTS CellTiter 96 Aqueous One Solution Cell Proliferation Assay. After a 2 h incubation at 37°C, absorbance is measured at 490 nm using a microplate spectrophotometer. Three biological replicates are performed for each cell line where each inhibitor(s)/Cisplatin concentration is assayed in triplicate for each experiment[2].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References

Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 2.1253 mL 10.6265 mL 21.2531 mL 53.1327 mL
5 mM 0.4251 mL 2.1253 mL 4.2506 mL 10.6265 mL
10 mM 0.2125 mL 1.0627 mL 2.1253 mL 5.3133 mL
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ETP-46464 Related Classifications

Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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ETP-46464
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